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Malignant Peritoneal Mesothelioma Treated by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is GLUT1 Expression a Major Prognostic Factor? A Preliminary Study

Authors:
J Hommell-Fontaine
J Hommell-Fontaine
J Hommell-Fontaine
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Soibi Isaac at Saint Thomas University
Soibi Isaac
Guillaume Passot at CHU de Lyon - Centre Hospitalier Lyon Sud
Guillaume Passot
Evelyne Decullier at Hospices Civils de Lyon (Centre Hospitalier Universitaire de Lyon)
Evelyne Decullier
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Abstract

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare primary peritoneal malignancy. Its prognosis has been improved by an aggressive locoregional treatment combining extensive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prognostic factors are currently poorly defined for this disease but are essential if treatment is to be standardized. Twenty-eight patients with DMPM, who were considered preoperatively to be candidates for CRS and HIPEC between June 1998 and August 2010 at our institution, were selected for this study. Medical records and histopathological features were retrospectively reviewed and 24 clinical, histological, and immunohistochemical parameters were assessed for their association with overall survival by univariate and multivariate analyses. The following factors were significantly associated with overall survival by univariate analysis: predominant histological growth pattern in the epithelioid areas, nuclear grooves in the epithelioid areas, atypical mitoses, and calretinin and GLUT1 expression by immunohistochemistry in the epithelioid areas. Expression of the facilitative glucose transporter protein GLUT1 in the epithelioid areas was the only factor independently associated with overall survival by multivariate analysis. GLUT1 expression appears to be an indicator of poor prognosis in DMPM. Standard histological classification of DMPM may not be adequate to select patients for aggressive locoregional treatments, such as CRS and HIPEC. Multicenter validation of the prognostic factors identified in this preliminary study is needed to refine patient selection for potential cure.
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ERRATUM
Erratum to: Malignant Peritoneal Mesothelioma Treated
by Cytoreductive Surgery and Hyperthermic Intraperitoneal
Chemotherapy: Is GLUT1 Expression a Major Prognostic
Factor? A Preliminary Study
J. Hommell-Fontaine, MD
1,5
, S. Isaac, MD
1,7
, G. Passot, MD
2,5,7
, E. Decullier, PhD
4,5,6
, A. Traverse-Glehen, MD,
PhD
1,5
, E. Cotte, MD, PhD
2,5,7
, B. You, MD, PhD
3,7
, F. Mohamed, MD
8
, F. N. Gilly, MD, PhD
2,5,7
, O. Glehen, MD,
PhD
2,5,7
, and F. Berger, MD, PhD
1,5
1
Service d’Anatomie Pathologique, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Be
´
nite, France;
2
Service
de Chirurgie Ge
´
ne
´
rale, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Be
´
nite, France;
3
Service d’Oncologie
Me
´
dicale, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Be
´
nite, France;
4
Unite
´
de me
´
thodologie en
recherche clinique, Hospices Civils de Lyon, Pole IMER, Lyon, France;
5
Universite
´
Lyon 1, Lyon, France;
6
Equipe
d’Accueil Sante
´
—Individu Socie
´
te
´
, Universite
´
de Lyon, Lyon, France;
7
Equipe d’Accueil EMR3738 Ciblage the
´
rapeutique
en oncologie, Universite
´
Lyon 1, Pierre-Be
´
nite, France;
8
National Pseudomyxoma Peritonei Centre, North Hampshire
Hospital, Hampshire, UK
ERRATUM TO: ANN SURG ONCOL (2013) 20:3892–3898
DOI 10.1245/S10434-013-3077-4
The authors’ affiliations are correct as presented in this
erratum. Figure 1 was incorrect in the original article. The
correct figure is as follows:
The online version of the original article can be found under doi:10.
1245/s10434-013-3077-4.
Ó Society of Surgical Oncology 2014
Published Online: 4 January 2014
O. Glehen, MD, PhD
e-mail: olivier.glehen@chu-lyon.fr
Ann Surg Oncol (2014) 21:S778–S779
DOI 10.1245/s10434-013-3389-4
FIG. 1 Overall survival of
patients with DMPM according
to the expression of GLUT1 in
immunohistochemistry. Patients
with expression of GLUT1
(C 5 %) had significantly worse
overall survival (log-rank,
P \ 0.0001)
Prognostic Factors in Peritoneal Mesothelioma S779
... It was demonstrated by Minato et al. that mesothelioma cells can upregulate GLUT-1 to uptake glucose more efficiently. Increased levels of GLUT-1 are often correlated with poorer prognoses [117,118]. In the mesothelioma microenvironment, the availability of glucose is critical, and competition for this molecule impacts on T-cell function and the recruitment of immune infiltrating cells, promoting angiogenesis [119][120][121][122]. ...
Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma
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  • Aug 2023
Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells’ transformation. Chronic inflammation supported by “frustrated” macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells’ features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor–host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.
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... The deregulated glucose metabolism in peritoneal cancers has been well-documented in several studies. In peritoneal mesothelioma, for example, studies have shown the increased expression of glucose transporter 1 (GLUT1) and its utility as a prognostic factor [40][41][42]. This upregulation of glucose transporter and hexokinase enables the cancer cells to take up more glucose and convert it into glucose-6-phosphate, the first step in glycolysis. Enhanced glucose uptake by GLUT1 also augments the TCA cyclemediated energy metabolism of the cancer cells. ...
Targeting Oncometabolites in Peritoneal Cancers: Preclinical Insights and Therapeutic Strategies
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  • Apr 2023
Peritoneal cancers present significant clinical challenges with poor prognosis. Understanding the role of cancer cell metabolism and cancer-promoting metabolites in peritoneal cancers can provide new insights into the mechanisms that drive tumor progression and can identify novel therapeutic targets and biomarkers for early detection, prognosis, and treatment response. Cancer cells dynamically reprogram their metabolism to facilitate tumor growth and overcome metabolic stress, with cancer-promoting metabolites such as kynurenines, lactate, and sphingosine-1-phosphate promoting cell proliferation, angiogenesis, and immune evasion. Targeting cancer-promoting metabolites could also lead to the development of effective combinatorial and adjuvant therapies involving metabolic inhibitors for the treatment of peritoneal cancers. With the observed metabolomic heterogeneity in cancer patients, defining peritoneal cancer metabolome and cancer-promoting metabolites holds great promise for improving outcomes for patients with peritoneal tumors and advancing the field of precision cancer medicine. This review provides an overview of the metabolic signatures of peritoneal cancer cells, explores the role of cancer-promoting metabolites as potential therapeutic targets, and discusses the implications for advancing precision cancer medicine in peritoneal cancers.
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... DMPM mostly remains localized in the abdominopelvic space throughout its course. The combination of CRS and HIPEC, applied for regional treatment, resulted significant improvement in treatment results [7][8][9][10]. This approach involves optimal operative tumor cytoreduction to improve efficacy of perioperative HIPEC as the penetration of HIPEC into peritoneal nodules is generally limited to [?] 3 mm [8]. ...
Nivolumab for Pediatric Malignant Peritoneal Mesothelioma
Preprint
Full-text available
  • Jun 2022
Mesothelioma is a rare and aggressive tumor originating from the serosal lining of the pleural, peritoneal and pericardial cavities. There are very few cases diagnosed with malignant peritoneal mesothelioma reported in childhood. Thanks to the developments in the field of immunotherapy, the prognosis of the disease has improved with the addition of the immune check point inhibitor, an anti-programmed death-1 monoclonal antibody, nivolumab to the treatment of MPM. In the treatment of our case who was diagnosed with diffuse malignant peritoneal mesothelioma at a very early age; cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, platinum and pemetrexed combination chemotherapy and nivolumab were used. Our patient, who has been on nivolumab therapy for 14 months and has been followed up for 20 months since her diagnosis, is still in remission. This case supports the utility of nivolumab in pediatric MPM.
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... In this study, CRS þ HIPEC to treat DMPM improved the median OS to 32.6 months, with a 30-day perioperative SAE (Table 5) [11][12][13][14][15][16][17][18][19][20][21][22][23]. These studies varied widely in terms of the sample size, pathological type, disease severity, and clinical outcomes. ...
Key factors for successful cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy to treat diffuse malignant peritoneal mesothelioma: results from specialized peritoneal cancer center in China
Article
Full-text available
  • Apr 2022
Objectives To investigate independent factors for the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of diffuse malignant peritoneal mesothelioma (DMPM). Methods The clinical database of 110 DMPM patients treated with CRS + HIPEC at our hospital was retrospectively analyzed. Independent prognostic factors were screened using univariate and multivariate analyses and the safety of the perioperative period was evaluated based on adverse events. Results Among the 110 patients with DMPM, 34 (30.9%) had a peritoneal cancer index (PCI) < 20 and 76 (69.1%) had PCI ≥20; 59 (53.6%) patients achieved completeness of cytoreduction (CC) 0/1 and 51 (46.4%) cases achieved CC 2/3. At the median follow-up of 43.3 (95%CI: 37.3–49.4) months, 48 (43.6%) patients were still alive and 62 (56.4%) patients died. The median overall survival was 32.6 months. Serious adverse events (SAEs) occurred in 41 patients (37.3%) and the perioperative mortality rate was 2.7%. Univariate analysis identified nine prognostic factors: Karnofsky performance status score, perioperative tumor markers, PCI, red blood cell infusion, pathological type, vascular tumor emboli, lymphatic metastasis, Ki-67 index, and perioperative SAEs (all p < 0.05). Multivariate analysis identified four independent prognostic factors: pathological type (p = 0.007), vascular tumor emboli (p = 0.044), Ki-67 index (p = 0.044), and SAEs (p = 0.004). Conclusions CRS + HIPEC for DMPM treatment resulted in prolonged survival with acceptable safety. Tumor pathology and SAEs are key factors for successful CRS + HIPEC.
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... And although the tunica vaginalis is an anatomic extension of the peritoneum, paratesticular mesotheliomas were excluded from this cohort, as available data indicate that they are clinicopathologically distinct from mesothelioma of the peritoneum proper [3]. 6. Numerous prognostic immunomarkers have been reported in single studies (including GLUT1, MUC1, BCL2, IMP3, EGFR, and PTEN) [49][50][51][52][53]. These were not included in our analysis, but may warrant further investigation. ...
Malignant peritoneal mesothelioma: prognostic significance of clinical and pathologic parameters and validation of a nuclear-grading system in a multi-institutional series of 225 cases
Article
  • Oct 2020
Malignant peritoneal mesothelioma historically carried a grim prognosis, but outcomes have improved substantially in recent decades. The prognostic significance of clinical, morphologic, and immunophenotypic features remains ill-defined. This multi-institutional cohort comprises 225 malignant peritoneal mesotheliomas, which were assessed for 21 clinical, morphologic, and immunohistochemical parameters. For epithelioid mesotheliomas, combining nuclear pleomorphism and mitotic index yielded a composite nuclear grade, using a previously standardized grading system. Correlation of clinical, morphologic, and immunohistochemical parameters with overall and disease-free survival was examined by univariate and multivariate analyses. On univariate analysis, longer overall survival was significantly associated with diagnosis after 2000 (P = 0.0001), age <60 years (P = 0.0001), ECOG performance status 0 or 1 (P = 0.01), absence of radiographic lymph-node metastasis (P = 0.04), cytoreduction surgery (P < 0.0001), hyperthermic intraperitoneal chemotherapy (P = 0.0001), peritoneal carcinomatosis index <27 (P = 0.01), absence of necrosis (P = 0.007), and epithelioid histotype (P < 0.0001). Among epithelioid malignant mesotheliomas only, longer overall survival was further associated with female sex (P = 0.03), tubulopapillary architecture (P = 0.005), low nuclear pleomorphism (P < 0.0001), low mitotic index (P = 0.0007), and low composite nuclear grade (P < 0.0001). On multivariate analyses, the low composite nuclear grade was independently associated with longer overall and disease-free survival (P < 0.0001). Our data further clarify the interactions of clinical and pathologic features in peritoneal mesothelioma prognosis and validate the prognostic significance of a standardized nuclear-grading system in epithelioid malignant mesothelioma of the peritoneum.
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... revealed that GLUT1 expression is an indicator of poor prognosis in diffuse MPeM. [35] To date, there have been reports of GLUT1 expression mainly in pleural mesothelioma and its differential diagnosis, but few in peritoneal mesothelioma. Our study found that GLUT1was expressed in 39 (65%) of 60 peritoneal mesothelioma specimens. ...
Osteopontin, GLUT1 and Ki67 expression in malignant peritoneal mesothelioma: Prognostic implications
Article
Full-text available
  • Jun 2020
Background Malignant peritoneal mesothelioma is the most common primary peritoneal neoplasm. The only universally recognised pathological prognostic factor is histopathological subtype. Prognostic markers based on patient features and clinical stages have been disappointing Methods The aim of our work is to assess the prognostic role of several clinicopathological features in a retrospective cohort of 60 patients diagnosed with peritoneal mesothelioma. These patients were centrally collected and were immunohistochemically analysed for the expression of OPN, GLUT1, and Ki‐67. Labelling was assessed by two pathologists. Complete clinical information and follow‐up were obtained from patients’ records. Results OPN expression was identified in 52 (86.6%) of 60 specimens, and GLUT1 in 39 (65%) of 60 specimens. Univariate Cox regression analysis showed that a lower PCI, tumour‐directed treatment (chemotherapy or surgery alone or in any combination), lower Ki‐67, GLUT1 and lower OPN expression had a statistically significant positive effect on OS. PCI (HR(hazard rate)=1.032 [95%CI: 1.000–1.067]; P =0.054) and tumour‐directed treatment (HR=0.211 [95%CI: 0.104–0.430]; P <0.001), ki‐67 (HR=22.326 [95%CI: 3.523–141.498]; P =0.003) and OPN (HR=7.268 [95%CI: 1.771–29.811]; P =0.009) retained independent prognostic significance in the multivariate analysis, all with a positive effect on OS with the exception of GLUT1. Conclusion OPN, KI67, treatment and PCI were independent indicators for overall survival, and a higher level of OPN expression correlated significantly with poorer OS This article is protected by copyright. All rights reserved.
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... Mesothelioma cells can upregulate Glucose Transporter 1 (Glut1) in order to more efficiently access glucose and this is evident on IHC (61). Elevated Glut1 levels has been recognized as a poor prognostic factor (62). Mesothelioma is typically a low glucose environment and glucose is reduced in mesothelioma-associated pleural effusions (63). ...
The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy
Article
Full-text available
  • Dec 2019
Although mesothelioma is the consequence of a protracted immune response to asbestos fibers and characterized by a clear immune infiltrate, novel immunotherapy approaches show less convincing results as compared to those seen in melanoma and non-small cell lung cancer. The immune suppressive microenvironment in mesothelioma is likely contributing to this therapy resistance. Therefore, it is important to explore the characteristics of the tumor microenvironment for explanations for this recalcitrant behavior. This review describes the stromal, cytokine, metabolic, and cellular milieu of mesothelioma, and attempts to make connection with the outcome of immunotherapy trials.
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Peritoneal Mesothelioma: Disease Biology and Patterns of Peritoneal Dissemination
Chapter
  • May 2020
Mesothelioma is a rare neoplasm arising from the mesothelial cells lining the pleura, peritoneum, pericardium, and tunica vaginalis layer of testis [1]. Diffuse malignant peritoneal mesothelioma (DMPM) represents about one-fifth to one-third of all forms of mesothelioma.
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Survivin expression as an independent predictor of overall survival in malignant peritoneal mesothelioma
Article
Full-text available
  • Apr 2020
Malignant peritoneal mesothelioma (MPeM) is an incurable cancer strongly associated with asbestos exposure and characterised by poor prognosis. The aim of the present study was to elucidate the prognostic and predictive value of CD146 and survivin expression in MPeM. Diagnostic biopsies from 60 patients with MPeM were collected and analysed for CD146, survivin and Ki-67 expression using immunohistochemistry. Complete clinical and follow-up information was obtained from patients' records. CD146 was expressed in 31/60 MPeM specimens and survivin in 34/60 specimens, with both expression levels being significantly associated with the Ki-67 labelling index (Ki-67LI). Kaplan-Meier and univariate Cox regression analyses revealed that a lower peritoneal cancer index (PCI), tumour-directed treatment, stage I, lower Ki-67LI and lower CD146 and survivin expression had a statistically positive effect on overall survival (OS). Cox regression analysis revealed that PCI [hazard ratio (HR)=1.99; 95% CI, 1.04-3.83; P=0.038], survivin (HR=1.47; 95% CI, 1.03-2.10; P=0.034) and treatment protocol including intraperitoneal chemotherapy (HR=0.28; 95% CI, 0.14-0.57; P=0.013) and systemic chemotherapy (HR=0.13; 95% CI, 0.04-0.42; P=0.013) retained independent prognostic significance for OS. All of these were included in the nomogram. Calibration curves showed good agreement between nomogram-predicted and observed survival. The C-index of the nomogram for predicting OS was 0.77. A lower PCI, intraperitoneal chemotherapy, systemic chemotherapy and a lower level of survivin were powerful prognostic markers in patients with MPeM. The proposed nomogram provides individual survival prediction for patients with MPeM.
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Immunohistochemical detection of GLUT-1 can discriminate between reactive mesothelium and malignant mesothelioma
Article
Full-text available
  • Dec 2006
The separation of benign reactive mesothelium (RM) from malignant mesothelial proliferation can be a major challenge. A number of markers have been proposed, including epithelial membrane antigen, p53 protein, and P-glycoprotein. To date, however, no immunohistochemical marker that allows unequivocal discrimination of RM from malignant pleural mesothelioma (MPM) has been available. A family of glucose transporter isoforms (GLUT), of which GLUT-1 is a member, facilitate the entry of glucose into cells. GLUT-1 is largely undetectable by immunohistochemistry in normal epithelial tissues and benign tumors, but is expressed in a variety of malignancies. Thus, the expression of GLUT-1 appears to be a potential marker of malignant transformation. Recently, in fact, some studies have shown that GLUT-1 expression is useful for distinguishing benign from malignant lesions. The purpose of the present study was to evaluate the diagnostic utility of GLUT-1 expression for diagnostic differentiation between RM and MPM. Immunohistochemical staining for GLUT-1 was performed in 40 cases of RM, 48 cases of MPM, and 58 cases of lung carcinoma. Immunohistochemical GLUT-1 expression was seen in 40 of 40 (100%) MPMs, and in all cases the expression was demonstrated by linear plasma membrane staining, sometimes with cytoplasmic staining in addition. GLUT-1 expression was also observed in 56 out of 58 (96.5%) lung carcinomas. On the other hand, no RM cases were positive for GLUT-1. GLUT-1 is a sensitive and specific immunohistochemical marker enabling differential diagnosis of RM from MPM, whereas it cannot discriminate MPM from lung carcinoma.Keywords: Glut-1, reactive methothelium, malignant pleural mesothelioma, immunohistochemistry, lung carcinoma
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Glucose transporter-1 in pulmonary neuroendocrine carcinomas: Expression and survival analysis
Article
Full-text available
  • Feb 2009
Glucose transporter-1 (GLUT-1) mediates the transport of glucose across the cellular membrane. Its elevated levels and/or activation have been shown to be associated with malignancy. The aim of this study was to investigate GLUT-1 expression in pulmonary neuroendocrine carcinomas. Tissue microarray-based samples of 178 neuroendocrine carcinomas, including 48 typical carcinoids, 31 atypical carcinoids, 27 large cell neuroendocrine carcinomas and 72 small cell carcinomas from different patients, were studied immunohistochemically for GLUT-1 expression. Forty-seven percent (75/161) of pulmonary neuroendocrine carcinomas were immunoreactive with GLUT-1. GLUT-1 was observed in 7% (3/46) of typical carcinoid, 21% (6/29) of atypical carcinoid, 74% (17/23) of large cell neuroendocrine carcinoma and 78% (49/63) of small cell carcinoma. GLUT-1 expression correlated with increasing patient age (P=0.01) and with neuroendocrine differentiation/tumor type (P<0.001), but not with gender, tumor size or stage. GLUT-1 expression was seen in a characteristic membranous pattern of staining along the luminal borders or adjacent to necrotic areas. GLUT-1 expression was associated with an increased risk of death for neuroendocrine carcinomas as a group (risk ratio=2.519; 95% confidence interval=1.519–4.178; P<0.001) and carcinoids (risk ratio=4.262; 95% confidence interval=1.472–12.343; P=0.01). In conclusion, GLUT-1 is expressed in approximately half of the pulmonary neuroendocrine carcinomas and shows a strong correlation with neuroendocrine differentiation/grade, but not with other clinicopathologic variables. Further studies appear plausible to elucidate the prognostic significance of GLUT-1 expression in pulmonary carcinoids.Keywords: GLUT-1, neuroendocrine carcinoma, carcinoid, survival, lung
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GLUT‐1 expression in ovarian carcinoma
Article
Full-text available
  • Sep 2001
  • CANCER-AM CANCER SOC
BACKGROUND Cancer cell growth is an energy-related process supported by an increased glucose metabolism. The objective of this study was to investigate the association of GLUT-1 with response to chemotherapy and outcome in patients with ovarian carcinoma.METHODS Histologic sections of formalin fixed, paraffin embedded specimens from 113 primary ovarian carcinomas were stained for GLUT-1 by using polyclonal GLUT-1 antibody (Dako Co., Carpinteria, CA) and the labeled streptavidin biotin procedure. Intensity of GLUT-1 staining was compared with disease free survival (DFS), chemotherapy response, and other clinicopathologic characteristics.RESULTSGLUT-1 cytoplasmic membrane staining was observed in 89 of 104 (85.6%) malignant tumors. Poorly differentiated tumors showed a trend to overexpress the GLUT-1 protein compared with the more differentiated counterparts (27.6% vs. 8.7%; P = 0.08). Patients who experienced a complete clinical response to chemotherapy were more frequently GLUT-1 positive than GLUT-1 negative (80% vs. 51.5%; P = 0.036). In multivariate analysis of advanced stage disease, residual tumor (P = 0.0001) and high GLUT-1 expression levels (P = 0.028) were the only independent variables that maintained a significant association with response to chemotherapy (P = 0.0001; chi-square = 38.13). In the subgroup of Stage III–IV (International Federation of Gynecology and Obstetrics patients showing a complete clinical response, GLUT-1 overexpression was associated with a shorter DFS. The median time to progression was 30 months in GLUT-1 strongly positive cases (> 50% of cancer cells positive) versus 60 months in GLUT-1 weakly positive cases (≤ 50% of cancer cells positive; P = 0.024).CONCLUSIONSGLUT-1 status is an independent prognostic factor of response to chemotherapy in advanced stage ovarian carcinoma. Moreover, patients overexpressing GLUT-1 show a significantly shorter DFS. These results suggest that the assessment of GLUT-1 status may provide clinically useful prognostic information in patients with ovarian carcinoma. Cancer 2001;92:1144–50. © 2001 American Cancer Society.
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Prognostic Significance of Histomorphologic Parameters in Diffuse Malignant Peritoneal Mesothelioma
Article
  • Nov 2006
Context.—Diffuse malignant peritoneal mesothelioma is currently regarded as a rare and lethal primary tumor arising from the peritoneal membrane. In the past, treatment plans with variable combinations of surgery and systemic chemotherapy were associated with a median survival of approximately 1 year. Standardized treatments using cytoreductive surgery and perioperative intraperitoneal chemotherapy have extended this survival. Objective.—To critically analyze the prognostic significance of histomorphologic parameters as a determinant of survival. Design.—Sixty-two consecutive patients with diffuse malignant peritoneal mesothelioma in whom data were prospectively accumulated were retrospectively analyzed by 14 different histomorphologic parameters. The influences of these pathologic characteristics on survival were critically statistically evaluated. Results.—In a univariate analysis, histologic type, nuclear/nucleolar size, stroma, depth of invasion into the bowel, atypical mitoses, mitotic index, necrosis, lymph node involvement, and chromatin patterns were found to be significant. In the multivariate analysis, histologic type and nuclear/nucleolar size remained as determinant histomorphologic characteristics. Use of biphasic/sarcomatoid histologic type as a poor prognostic characteristic was limited in that only 8% of patients showed this histology. Conclusions.—Histomorphologic parameters carry prognostic significance in predicting the survival of patients with diffuse malignant peritoneal mesothelioma when treated in a standardized fashion using cytoreductive surgery and perioperative intraperitoneal chemotherapy. Nuclear/nucleolar size was found to be a reliable histomorphologic assessment available to assess prognosis in these patients.
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Expression of glucose transporter‐1 in human gastric carcinoma
Article
  • Aug 2001
  • CANCER-AM CANCER SOC
Malignant cells show increased glucose uptake in vitro and in vivo, which is believed to be facilitated by glucose transporters (Gluts). Expression of Glut1, one of the Gluts, has been described in malignancies of the esophagus, colon, pancreas, lung, and brain, but to the authors' knowledge the significance of Glut1 expression in human gastric carcinoma has not been elucidated. The objective of the current study was to examine the expression and distribution of Glut1 and its relation to clinicopathologic parameters in patients with gastric carcinoma.
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GLUT1 glucose transporter expression in colorectal carcinoma
Article
  • Jul 1998
  • CANCER-AM CANCER SOC
BACKGROUND Malignant cells exhibit increased glycolytic metabolism, and in many cases increased glucose transporter gene expression. The authors hypothesized that GLUT1 glucose transporter expression is increased in colorectal carcinoma, and that the degree of expression might have prognostic significance.METHODSGLUT1 glucose transporter immunostaining was studied in normal colon and benign colon adenomas and in 112 colorectal carcinomas from patients for whom long term clinical outcome was known.RESULTSGLUT1 immunostaining was absent in normal colorectal epithelium and tubular adenomas, and absent or only weakly apparent in tubulovillous adenomas. The majority of carcinomas (101 of 112; 90%) had GLUT1 immunostaining. Tumors from 92 patients had low GLUT1 expression (< 50% of cells were GLUT1 positive) and 19 of these patients (21%) died of disease during follow-up. In contrast, tumors from 20 patients had high GLUT1 expression (> 50% of cells were GLUT1 positive) and 9 of these patients (45%) died of disease during follow-up. Disease specific mortality was greater in patients with high GLUT1 tumors (relative risk of 2.4; P = 0.02). In a multivariate analysis to assess whether high GLUT1 staining correlated with increased mortality independently of Dukes stage, the risk of death from colon carcinoma in the group with high GLUT1 staining was 2.3 times that in the group with low GLUT1 staining, a difference that approached statistical significance (P = 0.07).CONCLUSIONSGLUT1 glucose transporter expression is associated strongly with neoplastic progression in the colon, and assessment of the extent of GLUT1 immunostaining in colorectal carcinoma identifies patients with a poorer prognosis. Cancer 1998;83:34-40. © 1998 American Cancer Society.
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Utility of Glucose Transporter 1 in the Distinction of Benign and Malignant Thoracic and Abdominal Mesothelial Lesions
Article
  • Jul 2012
  • ARCH PATHOL LAB MED
Malignant mesothelioma, of either peritoneum or pleura, is an uncommon cancer. The diagnosis is often difficult to make, in part because of the overlapping morphology of reactive and malignant mesothelial cells. Glucose transporter 1 (GLUT-1) is a glucose transporter typically found on erythrocytes, which is aberrantly expressed in various carcinomas. It has recently been reported as specific and sensitive in discriminating malignant pleural mesothelioma from reactive hyperplasia. The application of GLUT-1 staining in peritoneal mesothelioma has not been fully explored. To determine if GLUT-1 staining is helpful in distinguishing abdominal mesotheliomas from benign, reactive mesothelial lesions and to further study its utility in the thorax. Tissue microarrays containing 135 abdominal malignant mesotheliomas and 30 malignant pleural mesotheliomas were stained with an antibody to GLUT-1, as were 56 reactive mesothelial lesions. The overall sensitivity and specificity for GLUT-1 in mesothelioma was 53% and 98%, respectively. The sensitivity in epithelioid malignant mesothelioma was 49% and in sarcomatoid/biphasic malignant mesothelioma, 66%. In the thorax, the sensitivity was 50% and in the abdomen it was 54%. The positive predictive value of GLUT-1 immunoreactivity was 98% and the negative predictive value was 40%. Glucose transporter 1 staining of thoracic mesotheliomas showed high specificity but lower sensitivity than previously reported. Abdominal malignant mesotheliomas showed similar results. Because of low sensitivity, only positive staining is informative. In both sites, the utility of the stain was limited by nonspecific staining (eg, in necrotic areas) as well as bright labeling of erythrocytes and occasional lymphoid elements. Despite these limitations, GLUT-1 can help differentiate malignant mesothelioma from reactive benign mesothelium.
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