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Sections of sinonasal inverted papilloma with minimal basal cell atypia (a HE stain) Immunostain b shows no expression of Fascin (score: 0). Insert shows a closer view
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Sinonasal inverted papilloma (IP) is a primary benign lesion with a tendency for local recurrence. Malignant transformation may develop in up to 15% of cases. Fascin (Fascin 1) is an actin cross-link binding protein required for the formation of actin-based cell-surface protrusions and cell motility. Fascin up-regulation in lung, gastric, breast an...
Contexts in source publication
Context 1
... normal squamous epithelium, fascin is only expressed in the cytoplasm of the basal layer cells (Fig. 1). Fascin positivity was seen in 26 of 47 specimens from 34 patients (55%). The Fascin immunostaining positivity was deter- mined by dark brown cytoplasmic stain in dysplastic cells, which is corresponding to the extent of dysplasia (Figs. 2, 3, 4). The distribution of final scores is summarized in Table 2. We collapsed the four categories into two: low- grade and no dysplasia versus high-grade dysplasia plus carcinoma in situ (Table 3). Cut-offs of either 3 and 4, or 4 and 5, were significant associated with high-grade dyspla- sia/carcinoma in situ (P = 0.0005 and 0.0001, respec- tively, Fischer exact ...
Context 2
... over-expression is associated with increased invasiveness of carcinomas in the urinary bladder [21,30], where benign proliferative lesions such as nephrogenic adenoma, IP, and exophytic papilloma were negative for fascin [21]. Its over-expression is seen more often in dysplastic epithelium in sinonasal IP, and may be organ specific. In our study, the fascin positive scores correspond to the percentage of immunoreactivity in the dysplastic cells. Increasing the percentages of fascin immunoreactive cells correlates to the extent of dysplasia (Figs. 1, 2, 3, ...
Citations
... Even the current WHO classification has not included "carcinoma ex sinonasal papilloma" among its topics, which might negatively affect the precise diagnosis of such a category [28]. It should also be noted that the IHC profile of this group is yet to be established, despite several IHC studies conducted in this context [27,[29][30][31][32][33][34][35][36][37][38][39][40]. ...
Sinonasal inverted papilloma (IP) has a propensity for malignant transformation. Although the IP-associated squamous cell carcinoma (SCC) is rare, it has a poor prognosis. To the best of our knowledge, this is the first study to assess IMP3 immunohistochemical (IHC) expression in sinonasal tumors and to compare it to the Ki-67 IHC expression and to other established clinicopathological parameters. A retrospective study was conducted on three groups which consisted of 72 cases of sinonasal IP, 20 age-matched samples of normal respiratory epithelium, and 15 cases of sinonasal SCC associated with IP, which were obtained from the archives of the Pathology Lab of Ain Shams University Specialized and Ain Shams University Hospitals during the period from January 2012 to December 2019. An IHC study was performed to evaluate IMP3 and Ki-67 expression in the three groups, with correlation of IMP3 expression to established clinicopathological parameters of sinonasal SCC on top of IP. Both IMP3 and Ki-67 showed a sharp rise in expression in the sinonasal SCC group. In addition, there were statistically significant differences in expression values between the 3 groups (). Receiver Operating Characteristic (ROC) analysis revealed that IMP3 and Ki-67 could be used to discriminate sinonasal SCC from control and IP lesions, with sensitivity and specificity of 100% and 81.5% for IMP3, respectively, and 100% and 62.5% for Ki-67, respectively. Spearman’s rho revealed that both IMP3 and Ki-67 were significantly related to the lymph node and tumor stages but not to the tumor grade. ROC analysis was performed to select cut-off scores for progression and survival for IMP3, and accordingly, Kaplan-Meier analysis showed correlation between IMP3 and overall survival, local recurrence-free survival, and metastasis-free survival in sinonasal SCC cases at the selected cut-off values. Based on our results, IMP3 could serve as a promising diagnostic, prognostic, and therapeutic marker for IP-associated sinonasal SCC.
1. Introduction
Sinonasal inverted papilloma (IP) is one of the most common nonmalignant lesions in the nasal cavity and paranasal sinuses. Although benign, it has a high recurrence rate (up to 78% of cases), destroys surrounding structures (including bone erosion and orbital wall involvement), and may undergo malignant transformation (in 5–15% of cases). In fact, sinonasal IPs are concomitantly diagnosed in 1.7–56% of patients with sinonasal squamous cell carcinoma (SCC). Moreover, malignant transformation in such lesions has worse long-term clinical outcomes that include metastasis, postoperative disfigurement, and/or death [1–3]. Thus, precise and early diagnosis, thorough follow-ups, and discovering new prognostic and therapeutic indicators have become necessary in the management of sinonasal IP.
The oncofetal RNA-binding protein insulin-like growth factor 2 mRNA binding protein 3 (IMP3) is expressed during the early stages of embryogenesis and plays a role in cell growth and migration. These functions are mediated by posttranscriptional regulation of cell proliferation via regulation of IGF-2 transcription. After birth, IMP3 becomes epigenetically silenced, such that normal adult tissues show no detectable expression of this protein. However, its reexpression was noted in a series of human malignancies but not in the adjacent normal epithelium [4–6]. Moreover, several studies have demonstrated a prognostic role for IMP3 in several malignancies and their progression [7–13].
Only a few studies have assessed the immunohistochemical (IHC) expression of IMP3 in head and neck SCC [6, 14–18], and none have been conducted on sinonasal tumors. Thus, the primary objectives of the current study were to evaluate the IHC expression of IMP3 in the normal sinonasal epithelium, sinonasal IP, and IP-associated sinonasal SCC and to analyze its expression in relation to Ki-67 being an established biomarker. A secondary objective is comparing the IHC expression of IMP3 to established clinicopathological parameters of SCC on top of IP.
2. Materials and Methods
2.1. Tissue and Patient Data
The current study was a retrospective study conducted on three groups: 72 cases of sinonasal IP, 20 age-matched samples of normal respiratory epithelium obtained from cases with inflammatory/allergic nasal polypi and cases submitted to exclude fungal infection that proved to be free of fungal infection by periodic acid Schiff, and 15 cases of sinonasal SCC associated with IP. They were obtained from the archives of the Pathology Lab of Ain Shams University Specialized and Ain Shams University Hospitals. These were received and diagnosed during the period from January 2012 to December 2019. All cases underwent surgical intervention such as transnasal endoscopic resection and open surgical resection. The archival files were reviewed to determine the age and sex of patients. Hematoxylin and Eosin (H&E) stained slides were examined to reevaluate and verify the histopathologic diagnosis and histologic grade according to the World Health Organization (WHO) tumor differentiation [19–21]. TNM staging was performed according to the American Joint Committee on Cancer (AJCC) [22]. Normal sinonasal respiratory epithelial samples were also confirmed by histology.
ENT reports of the patients of the third group of IP-associated SCC were reviewed to determine (a) survival time, which was calculated based on the date of major surgery and the date of last follow-up or death, and (b) progression-free survival time, which was calculated based on the date of major surgery or last session of adjuvant postoperative radiotherapy and the date of relapse (local recurrence/distant metastasis) at the last follow-up.
2.1.1. Ethics Statement
Signed written and informed consent was obtained from all participants prior to surgery. The study was approved by the Research Ethical Committee at the Faculty of Medicine, Ain Shams University.
2.1.2. Immunohistochemical Staining
Four-micrometer sections of formalin-fixed and paraffin-embedded samples of normal respiratory epithelium, sinonasal IP, and sinonasal SCC associated with IP were prepared. IHC staining was performed on samples of the three groups using rabbit monoclonal anti-IMP3 (Clone: EP286; Cell Marque, Sigma-Aldrich Co., California, USA; 1 : 100 dilution) and rabbit monoclonal anti-Ki-67 (Clone: SP6; Cell Marque, Sigma-Aldrich Co., California, USA; 1 : 200 dilution). Avidin-Biotin immunoperoxidase complex technique was used by applying the sensitive detection kit (BioGenex, Fermont, California, USA) [23]. This was followed by fixation on poly-L-lysine-coated slides overnight at 37° C. They were then deparaffinized and rehydrated using graded alcohol series. Heating of the sections in a microwave oven in 10 mM citrate buffer (pH 6.0) was performed for 20 minutes. Blocking of endogenous peroxidase, incubation in Protein Block Serum-Free Solution (DakoCytomation, Glostrup, Denmark) for 20 minutes, then incubation overnight at 4°C with primary antibodies were done. Addition of biotinylated anti-mouse immunoglobulin and streptavidin conjugated to horseradish peroxidase was then performed. Finally, 3,3-diaminobenzidine as the substrate or chromogen was used to form an insoluble brown product. The sections were counterstained with hematoxylin and mounted. Sections of pancreatic ductal adenocarcinoma samples were used as positive control for IMP3 while sections of tonsillar tissue were used as positive control for Ki-67, with each run of every staining procedure performed. Negative control sections of each lesion were incubated with normal mouse serum instead of each of the primary antibodies.
2.1.3. Interpretation of Immunohistochemical Staining
IHC analysis of IMP3 and Ki-67 were blindly performed by three pathologists (the authors). Cytoplasmic staining of IMP3 and nuclear staining of Ki-67 in cells in any of the lesions of the three groups were regarded as positive staining. Slides were scanned by three pathologists at 20x magnification to identify representative hot spots for counting positive cells. The counting of cells with cytoplasmic positivity for IMP3 and cells with nuclear positivity for Ki-67 was performed at 400x magnification. Next, the proportion of positive cells over the total number of counted cells was independently estimated by each of the three pathologists, and the average was calculated. A multiheaded microscope was used to resolve any discrepancies.
The assessment of the intensity of cytoplasmic staining of IMP3 and the nuclear staining of Ki-67 was carried out by subjective consideration of staining intensity, which was scored as follows: 0: negative, 1: weak positivity, 2: moderate positivity, and 3: strong positivity. Any discrepancies were resolved by consensus using a multiheaded microscope [6].
All readings were performed independently and without any prior knowledge of the clinical or histopathological characteristics of the cases.
2.2. Statistical Analysis
Data was tested for normality with a Shapiro-Wilk test and expressed as for parametric numerical data or median (interquartile range) for nonparametric numerical data. Categorical variables were expressed as frequencies and percent. Student’s test or Mann-Whitney test was used to compare quantitative data between two groups according to data distribution. ANOVA or Kruskal-Wallis tests with post hoc test were used to compare quantitative data between two and more than 2 group tests according to data distribution. Spearman correlation analysis was used to test the strength of correlation between two variables. The ROC curve was used to evaluate the sensitivity and specificity of IMP3 and Ki-67 in predicting SCC. Multivariate logistic regression analysis was performed for determining the predictors of SCC. A significance level of was used in all tests. All statistical procedures were carried out using SPSS version 20 for Windows (SPSS Inc., Chicago, IL, USA).
3. Results
3.1. Patients
Data describing age and gender of the three studied groups are demonstrated in Table 1.
Group
Normal epithelium
Inverted papilloma
SCC
Mean
±SD
Mean
±SD
Mean
±SD
Age
47.95
6.03
48.43
5.42
57.80
9.30
Gender
Male
9
45.0%
49
68.1%
13
86.7%
Female
11
55.0%
23
31.9%
2
13.3%
SD: standard deviation; SCC: squamous cell carcinoma.
... Two retrospective studies examined the association between fascin and IP-SCC by using immunohistochemical staining of specimens taken from different groups: IP, IP with high dysplasia, IP with SCC and normal control tissue. It was found that fascin expression increased gradually and significantly with the progression and severity of dysplasia [57][58][59]. ...
Background:
Inverted papilloma (IP) is an unusual type of benign tumor that has high recurrence rates and the potential to transform into squamous cell carcinomas (SCC). The mechanism of the transformation process from IP to IP-SCC is uncertain and there is no consensus regarding the best practice for IP-SCC detection. The goal of this study is to identify the best clinical methods to detect for IP-SCC.
Methods:
An evidence-based review was performed using Medline and Ovid to obtain all articles up to October 10th, 2019 pertaining to identification of IP malignant transformation. All manuscripts discussing clinical methods or biomarkers were included.
Results:
Based on clinical research studies, convoluted cerebriform pattern and apparent diffusion coefficient values on Magnetic Resonance Imaging (MRI) can help differentiate benign IP from SCC and increased SUVmax on PET/CT is associated with higher probability of malignancy although not as specific. No consensus about the best biomarker for IP-SCC has been reached among researchers and continues to be exploratory.
Conclusion:
Endoscopy with biopsy is the gold standard practice to identify IP-SCC; however, MRI is the preferred imaging modality to recognize malignant transformation in cases where biopsy is difficult. Multiple biomarkers have shown positive results, but no single indicator with clinical significance for monitoring malignant transformation process has been found.
... 34,36,37 A number of genetic and molecular alterations have been studied to define the molecular basis of progression from IP to SCC, whereas little is known about the biological profile of dysplastic IP. 3,38 HPV DNA, fascin, and p53 expression were found to be significantly increased in IPs with dysplasia. 39,40 Although the role of HPV in IP still remains controversial, [41][42][43][44] recent evidence suggests that only a small subset of IPs are related to HPV in terms of etiology and cancerization. 21,45 It is reasonable that genetic changes promoting IP cancerization could provide gains of function that increase the aggressiveness of dysplastic IP, thus explaining the propensity to recur. ...
Background:
The technique for transnasal endoscopic resection of inverted papilloma (IP) has evolved considerably during the last 20 years. The aim of the present study is to retrospectively analyze a single tertiary center series, with special emphasis on assessing the value of an "insertion-driven" technique on local control.
Methods:
Patients undergoing endoscopic resection for IP at the University of Brescia during the period 1991 to 2015 were enrolled. Site of origin and extension of IPs were assessed, together with presence of dysplasia and carcinoma in situ. Patients were divided in 3 cohorts: (1) historical cohort (treated before 2008), (2) contemporary "centripetal" cohort (treated with a traditional technique after 2008), and (3) contemporary "insertion-driven" cohort (treated with insertion-driven resection). Groups were compared considering outcomes and complications.
Results:
The series included 210 patients. Mean follow-up was 77.8 months. Thirty-eight (18.1%) patients showed precancerous changes. Maxillary involvement (p = 0.021) and presence of precancerous changes (p = 0.013) were significantly associated with a higher risk of recurrence. Five-year local control rate before and after 2008 was 95.1% and 90.5%, respectively. The insertion-driven cohort was associated with lower disease control when IPs involved the maxillary sinus. The rate of complications was 11.9%. The insertion-driven cohort was associated with a lower rate of major complications (p = 0.098).
Conclusion:
Preoperative evidence of precancerous changes and/or involvement of maxillary sinus should prompt the surgeon to address the disease more aggressively (centripetal resection). Preoperative imaging and biopsy with abundant material may optimize the chance to stratify patients eligible for less or more conservative approaches.
... Cell mobility is increased in various transformed epithelial cells. Fascin overexpression is significantly more common in SNIPs with high-grade dysplasia than in those with no dysplastic or low-grade dysplastic epithelium and may be associated with tumor progression and malignant transformation [39]. ...
Schneiderian papillomas are uncommon tumors which may develop within the nasal cavity and comprise three well-defined histological types: sinonasal inverted papilloma (SNIP), exophytic papilloma, and oncocytic papilloma. It is well known the rate of Schneiderian papilloma may also present a malignant degeneration and SNIP represents the most important subgroup in consideration of its frequency and malignant propensity. Although HPV infection is always considered the first event favoring the development of SNIP, however, it is not established as an eventual connection between viral actions and malignant transformation. In fact, different molecular mechanisms are suspected to play a crucial role in this process and, currently, many authors agree that only by improving our knowledge about these mechanisms it will be possible to achieve new and effective targeted therapies. So the aim of this study was firstly to systematically review the literature focusing on different biomarkers that could be implicated in the stages of SNIP malignant degeneration. Secondly, a systematic review with meta-analysis was performed to better define the incidence of sinonasal malignancies originating from Schneiderian papilloma (SNIP, exophytic papilloma, and oncocytic papilloma). Twenty-nine studies comprising a total of 3177 patients were statistically analyzed. Results showed a 9% (95% CI = 7–11) overall rate of malignant transformation from Schneiderian papilloma. In conclusion, this analysis confirmed that the potential malignancy of Schneiderian papilloma should not be underestimated. On the other hand, our review showed the paucity of studies investigating the molecular alterations which may be related with the malignant transformation of SNIP.
... To date, many studies have aimed to resolve this issue (Tables II and III CCAAT enhancer binding proteins (71), cyclooxygenase-2 (COX-2) (72), angiomotin (73), phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase (PTEN) (74), hypoxia-inducible factor 1-α (HIF-1α) (74), HPV infection and stathmin (75). Malignant transformation of SIP may be associated with the following factors: HPV 16/18 infection (76), epidermal growth factor receptor (EGFR) 1 (77,78); cell cycle proteins [p21 (79); p16 (79,80); p53 (80,81); p63 (79,81); p27; cyclin D1 (82); proliferating cell nuclear antigen reverse transcription (65,83); Ki-67 (65,84); metallothionein-2-5A/G (reference single nucleotide polymorphisms cluster ID, 28366003) (85); TFPI-2 (86); fascin (87); matrix metallopeptidase-2 (76); sex determining region Y-box 2 (88); topoisomerase II-α (84,89,90); OPN (91); homeobox protein MSX-2 (89-91); desmoglein 3 (92); survivin (83,93); cathepsin S (94); stefin A (94); E-cadherin (95); β-catenin (82,95); COX-2 (96,97); deleted in lung and esophageal cancer protein 1 (98); IQ motif containing GTPase activating protein 1 (99); Smac (93); PTEN (74); HIF-1α (74); Dvl-1 (82); retinoblastoma protein (100); and regulatory T cells (101). However, there were several key limitations in these studies. ...
Sinonasal inverted papilloma (SIP) is a benign tumor of the nasal cavity and sinus. SIP is characterized by aggressive malignant transformation and a high rate of recurrence. Inadequate removal of the tumor during surgery is one of the most significant contributors to SIP recurrence. A growing body of evidence suggests that molecular alteration in SIP, including human papilloma virus infections, single nucleotide polymorphisms of key genes, deregulation of signaling pathways and immunological changes, may lead to SIP occurrence and malignant transformation. However, the extent to which these molecular mechanisms contribute to SIP pathology and transformation remains unclear due to limited research. Further studies are warranted to elucidate the primary dependent factors that contribute to SIP etiology. The present article reviewed risk factors of progression and recurrence of SIP, including outdoor and industrial occupational exposure, smoking, septal deviation, SIP location, recurrent cases, stage of SIP-associated squamous cell carcinoma and choice of surgical method.
... 5,7,8 Recently, fascin expression in the neoplasms of thyroid cancer, oesophageal squamous cell carcinoma (SCC), oral cavity SCC, nasal inverted papilloma, laryngeal SCC, breast cancer, urothelial carcinomas of the urinary bladder, pancreatic adenocarcinoma and hepatocellular carcinoma has been reported to be associated with invasion of tumour cells and clinically aggressive manifestations. [9][10][11][12][13][14][15][16][17] No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease. ...
... 19 Recently, increased expression of fascin has been demonstrated in various human tumours and is correlated with invasion of tumour cells and clinically more aggressive manifestations. [9][10][11][12][13][14][15][16][17] Takikita et al. 10 studied 257 oesophageal specimens and found that positive fascin immunostaining increased progressively from normal tissue (26%) to dysplasia (45%) to oesophageal squamous cell carcinoma (69%). Chen et al. 9 studied thyroid samples from 177 cases and found that fascin immunoreactivity was negative in normal follicles and nodular goitre. ...
Objective
Fascin is an actin-bundling protein found in cell membrane protrusions and increases cell motility. The expression of fascin in epithelial neoplasms has been described only recently. No data are available concerning the role of this protein in invasive cholesteatoma. Thus, we investigated the expression of fascin in cholesteatoma tissue and the relationship between fascin expression and intraoperative evaluation of the destruction of the ossicular chain and extent of disease.Method
Cholesteatoma specimens of 28 patients and external auditory canal (EAC) skin specimens of the same patients (as the control group) were collected from mastoidectomies. Immunohistochemical technique was used to investigate the fascin expression all cholesteatoma tissues and EAC skin specimens Immunohistochemical staining was assessed semiquantitatively based on the thickness of epithelium. SPSS software version 16.0 (SPSS Inc., Chicago, IL, USA) was performed to statistically analyze the relationships between fascin expression and intraoperative evaluation destruction of ossicular chain and extent of the disease.ResultsImmunohistochemically, there was no or very low Fascin expression observed in normal epithelial cells of EAC skin, while expressed in cholesteatoma tissue. Also, Fascin expression in cholesteatoma tissues were significantly correlated with destruction of ossicular chain and extent of the disease.Conclusions
Fascin expression is usually found in cholesteatoma epithelium and is correlated with destruction of the ossicular chain and extent of disease. Considering all of the correlations between the clinical and histopathological findings, “fascin immunoexpression scoring” may be used for histological grading of cholesteatom.This article is protected by copyright. All rights reserved.
... HPV infection may be an early event in a multistep process of malignant formation of IP [110,139,140,143,144,164,179,523,524]. Precancerous lesions of IP exhibit elevated levels of fascin that may be associated with carcinogenesis of IP [525,526]. ...
Skull base inverted papilloma (IP) is an unusual entity for many neurosurgeons. IP is renowned for its high rate of recurrence, its ability to cause local destruction, and its association with malignancy. This paper is a comprehensive review of the reports, studies, and reviews published in the current biomedical literature from 1947 to September 2010 and synthesize this information to focus on its potential invasion to the base of the skull and possible intradural extension. The objective is to familiarize the clinician with the different aspects of this unusual disease. The role of modern diagnostic tools in medical imaging in order to assess clearly the limits of the tumors and to enhance the efficiency and the safety in the choice of a surgical approach is pointed out. The treatment guidelines for IP have undergone a complex evolution that continues today. Radical excision of the tumour is technically difficult and often incomplete. Successful management of IP requires resection of the affected mucosa which could be achieved with open surgery, endoscopic, or combined approach. Radio and chemotherapy were used for certain indications. More optimally research would be a multicenter randomized trials with large size cohorts.
... Fascin expression has been evaluated in several human neoplasia, and recently in epithelial tumours [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30], but to our knowledge only two studies have been conducted on the significance of fascin expression in endometrioid carcinomas [31,32]. With regard to CD44 and its variants, several studies have investigated its expressions in endometrial pathologies, including adenocarcinomas, yielding different results [31][32][33][34][35][36][37][38][39][40][41]. ...
Fascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters.
Fascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed.
The expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters.
Our findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899.
Background:
The mechanism underlying the malignant transformation of inverted papilloma (IP) has not yet been elucidated.
Methods:
To clarify the genes responsible for the malignant transformation, we analyzed 10 cases of IP, 8 of IP with dysplasia, and 11 of squamous cell carcinoma (SCC) by targeted amplicon sequencing.
Results:
The number of mutant genes increased in the order of IP < dysplasia < SCC. Significant differences were observed in the mutation rates of three genes (KRAS, APC and STK11) in particular. TP53 was altered frequently in each group and might be involved in malignant transformation based on to the site of the mutation. A comparison of the genetic variants by region of IP tissue among patients with IP alone, and those with dysplasia or SCC revealed significant differences in the mutation rate of the KRAS gene.
Conclusion:
Identification of genetic mutations in KRAS is effective for predicting the malignant transformation of IP.
