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Grading of interstitial fibrosis (IF) in papillary thyroid carcinoma, Hematoxylin and eosin staining. No/mild IF (A-C), 50×; moderate/severe IF (D-F), 100×.
Source publication
We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor–node–metastasis (pTNM) stage and age (p < 0.05). The overall survival was longer in p16-negative patients (195.73 vs....
Contexts in source publication
Context 1
... was no/mild in 108 cases (40.9%) (Fig. 3A-C) and moderate/severe in 156 (59.1%) ( Fig. 3D-F). The relationships between the degree of IF in cancer tissues and other clinicopathological parameters are shown in Table 1. Univariate survival analysis showed that RFS was significantly longer in the moderate/severe IF group than in the no/mild IF group (158.37 vs. 129.23 months, p = ...
Context 2
... was no/mild in 108 cases (40.9%) (Fig. 3A-C) and moderate/severe in 156 (59.1%) ( Fig. 3D-F). The relationships between the degree of IF in cancer tissues and other clinicopathological parameters are shown in Table 1. Univariate survival analysis showed that RFS was significantly longer in the moderate/severe IF group than in the no/mild IF group (158.37 vs. 129.23 months, p = 0.020, Fig. 4). OS was not significant different ...
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Objective
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Methods
The clinicopathological data and prognostic information of p...
Citations
... The CDKN2A (also known as ARF, INK4A, MTS-1) encodes two tumor suppressor proteins p16INK4A and p14ARF [60]. Previous study reported that high p16INK4A expression in PTC was associated with poor prognosis [61], and our findings suggested that CDKN2A was a risk factor for PTC patients. Based on a meta-analysis of 734 PTC patients, it was found that cancer tissues had significantly more CDKN2A promoter methylation than benign and normal tissues [62]. ...
Senescence-induced therapy was previously considered as an effective treatment for tumors, and cellular senescence was initially regarded as an effective mechanism against cancer. However, whether cell senescence-related genes can be used to predict the prognosis of papillary thyroid carcinoma (PTC) and immunotherapy remains unclear. We developed and validated a cell senescence-related signature (CSRS) by analyzing the gene expression of 278 genes related to cellular senescence in 738 patients with PTC. Additionally, further analysis showed that CSRS was a reliable predictor of patient outcomes in combination with immune checkpoint expression and drug susceptibility, and patients with high risk scores may benefit from immunotherapy. The findings of this study demonstrate that CSRS serves as an immunotherapeutic response and prognosis biomarker affecting the tumor immune microenvironment of PTC.
... The secretion of SASP factors by primary fibrotic mouse alveolar epithelial type II cells has also been confirmed in vitro [47]. In the thyroid, the severity of fibrosis is significantly low in p16negative papillary thyroid carcinoma compared to p16positive papillary thyroid carcinoma [48]. These reports suggested that p16 expression is involved in the formation of fibrosis, supporting our present data. ...
Background:
Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC.
Methods:
We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC . The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis.
Results:
Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41-12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08-4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59-3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36-5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34-6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001).
Conclusions:
Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes.
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Papillary thyroid carcinoma (PTC) is considered an indolent neoplasm but it may demonstrate aggressive behavior. We aimed to identify clinical and pathological characteristics and molecular signatures associated with aggressive forms of PTCs. We selected 43 aggressive PTC cases based on the presence of metastases at the time of diagnosis, the development of distant metastasis during follow-up, and/or biochemical recurrence, and 43 PTC patients that were disease-free upon follow-up, matching them according to age, sex, pT, and pN parameters. Twenty-four pairs (a total of 48 cases) and 6 normal thyroid tissues were studied using targeted mRNA screening of cancer-associated genes employing NanoString nCounter® technology. In general, aggressive PTCs showed distinctive clinical and morphological features. Among adverse prognostic parameters, the presence of necrosis and an increased mitotic index were associated with shorter disease-free and overall survivals. Other parameters associated with shorter disease-free or overall survivals include a lack of tumor capsule, the presence of vascular invasion, tumor-infiltrating lymphocytes, fibrosclerotic changes, age > 55 years, and a high pTN stage. Various pathways were differentially regulated in non-aggressive as compared to aggressive PTC, including the DNA damage repair, the MAPK, and the RAS pathways. In particular, the hedgehog pathway was differentially de-regulated in aggressive PTC as compared to non-aggressive PTC cases, being WNT10A and GLI3 genes significantly up- and down-regulated in aggressive PTC and GSK3B up-regulated in non-aggressive PTC cases. In conclusion, our study revealed specific molecular signatures and morphological features in aggressive PTC that may be useful to predict more aggressive behavior in a subset of PTC patients. These findings may be useful when developing novel, tailored treatment options for these patients.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12022-023-09769-x.
