Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix

Yajima, Nobuhisa; Wada, Ryuichi; Yamagishi, Shin‐Ichiro; Mizukami, Hiroki; Itabashi, Chieko; Yagihashi, Soroku

doi:10.1016/j.humpath.2005.08.022

Cited by 22 publications

(22 citation statements)

References 21 publications

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“…Our series contains 8 cases with complete loss of p53 expression, in three of which cases harbored p53 mutations. Since nonneoplastic appendiceal tissues show sporadic nuclear immunopositivity of p53 protein in low frequency (about 2%) [34], these cases with complete loss of p53 expression may represent loss of p53 function caused by TP53 mutations with possible deletion of another allele which is not identified in our PCR analysis. Furthermore, it has been shown that some p53 mutant variants have no effect on cell proliferation or cell viability [35], and do not influence the transcriptional activity of p21/WAF1, MDM2, or Bax promoters [36].…”

Section: Discussionmentioning

confidence: 85%

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Hara

Saito

Hayashi

et al. 2015

Pathology - Research and Practice

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Section: Discussionmentioning

confidence: 85%

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Hara

Saito

Hayashi

et al. 2015

Pathology - Research and Practice

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“…To the best of our knowledge, limited information is available on mucin, E-cadherin, and p53 immunoexpression patterns focusing on both benign and malignant tumors. 26 We propose that the number of altered protein markers, p53 status, NF-kB status, and b-catenin status are of clinical significance in appendiceal mucinous adenocarcinomas. In other words, p53 overexpression may signify shorter periods of disease-free survival and overall survival of patients.…”

Section: Discussionmentioning

confidence: 97%

“…3 Molecular changes, such as protein alterations, which may correspond with the biologic behavior of tumors, are helpful in classifying tumors and predicting clinical outcome. Following examination of the existing literature for immunoexpression data on proteins in mucinous neoplasms of various organs, including colorectum, [13][14][15][16][17][18] pancreas, 19,20 ovary, [21][22][23] and appendix, [24][25][26] we focused on 24 proteins. The immunoexpression profiles of different functional proteins in three groups-mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma of the appendix-were analyzed.…”

mentioning

confidence: 99%

Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors

et al. 2009

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Appendiceal mucinous neoplasms have been the focus of considerable debate in recent years. We histologically classified 70 appendiceal mucinous neoplasms into three categories: 32 mucinous adenoma, 23 mucinous neoplasm of uncertain malignant potential, and 15 mucinous adenocarcinomas. Immunohistochemistry was performed for 24 proteins in different functional categories, specifically, oncogenic proteins (bcl-2, b-catenin, CEA, C-erbB2, c-kit, Cox-2, Cyclin D1, EGFR, Ki-67, NF-jB, VEGF), tumor suppressors (E-cadherin, FHIT, hMLH1, p53, p63, smad4), cell-cycle regulators (p21, p27, p16), and mucin proteins (MUC1, MUC2, MUC5AC, MUC6). Our data showed that 9 out of the 24 proteins were more frequently altered in the mucinous adenocarcinoma group than in the mucinous adenoma group (Po0.05), including b-catenin (13% in mucinous adenoma vs 60% in mucinous adenocarcinoma), CyclinD1 (44 vs 87%), Ki-67 (high labeling index: 31 vs 67%), NF-jB (19 vs 60%), VEGF (16 vs 87%), E-cadherin (0 vs 47%), p53 (6 vs 40%), MUC2 (9 vs 67%), and MUC5AC (3 vs 40%). The distinct immunoexpression profile of mucinous neoplasm of uncertain malignant potential was placed between those of mucinous adenoma and mucinous adenocarcinoma (Po0.05). Moreover, the mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma categories displayed differences in terms of the number of altered markers among the nine proteins (Po0.05; mean 1.4 vs 2.6 vs 5.5, respectively). In mucinous adenocarcinoma, the p53 status was related to disease-free survival and overall survival of patients (Po0.05, both). NF-jB status and the number of altered protein markers made statistically marginal impacts on disease-free survival; also b-catenin loss, on overall survival of patients. In conclusion, protein immunoexpression profiles may facilitate the classification of appendiceal mucinous neoplasms. In our study, the three tumor categories of mucinous adenoma, mucinous neoplasm of uncertain malignant potential, and mucinous adenocarcinoma exhibited distinct immunoexpression profiles. Five and more altered protein markers, p53 overexpression, NF-jB positivity, and b-catenin loss were predictive factors of adverse clinical outcomes in appendiceal mucinous adenocarcinomas.

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“…This immunophenotypic variability suggests that there are at least 2 general categories of mucinous tumors in teratomas: those that would be compatible with a predominantly gastric or usual surface epithelial phenotype and those that would be more compatible with an appendiceal or lower enteric phenotype. 16,21,27,29 The majority of nonenteric immunophenotypes in the mucinous cystadenoma group were associated with varied epithelial morphologies that included nonspecific low cuboidal, stratified columnar, and gastric types. These findings support the concept that these mucinous tumors may arise from different epithelial types within the teratoma, not exclusively from the colonic or appendiceal type epithelium, and that they may not necessarily originate from the ovarian surface-type epithelium in a significant proportion of cases.…”

Section: Discussionmentioning

confidence: 99%

Ovarian Mature Teratomas With Mucinous Epithelial Neoplasms: Morphologic Heterogeneity and Association With Pseudomyxoma Peritonei

McKenney

Soslow

Longacre

2008

American Journal of Surgical Pathology

129

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Mucinous epithelial neoplasms arising in association with mature teratomas are a heterogeneous group of tumors, but with the exception of a single recent study, their full histologic spectrum, detailed immunophenotype, and association with classic pseudomyxoma peritonei (PMP) have not been fully studied. The morphologic, immunohistochemical, and clinical features of 42 patients with mucinous epithelial tumors arising in association with mature ovarian teratomas were evaluated. The patients' ages ranged from 17 to 66 years (mean, 39 y). Tumor size ranged from 5.5 to greater than 200 cm. Most teratoma-associated mucinous tumors were unilateral, although 1 patient harbored bilateral mucinous tumors in association with bilateral teratomas. In all cases, the teratomatous component consisted of mature elements. Using the 2003 World Health Organization criteria for ovarian intestinal type mucinous neoplasms, 17 (40%) were classified as mucinous cystadenoma, 16 (38%) as intestinal-type mucinous epithelial neoplasm of low malignant potential (IM-LMP), 4 (10%) as intraepithelial carcinoma (IEC), and 5 (12%) as invasive mucinous carcinoma. Mucinous cystadenomas had a varied epithelial lining consisting of lower gastroenteric, gastric foveolar, or müllerian appearance. In contrast, the IM-LMP, IEC, and invasive carcinoma cases had a more uniform lower gastroenteric histology. For mucinous cystadenomas, a cytokeratin (CK) 7+/CK20- phenotype (5/13; 38%) was equally as common as a CK7-/CK20+ phenotype (5/13; 38%), with the remaining cases coexpressing both keratins (CK7+/CK20+: 3/13; 23%). In contrast, IM-LMP, IEC, and invasive adenocarcinomas more frequently had a CK7-/CK20+ phenotype (56%, 50%, and 100%, respectively). A CK7+/CK20-phenotype was rare in these later 3 morphologic groups (6%). Of the 42 total cases, 55% had pseudomyxoma ovarii and 24% had classic PMP (1 cystadenoma, 6 IM-LMP, and 3 invasive carcinomas), whereas 5% had more localized accumulations of peritoneal mucin (both IM-LMP). Pathologic evaluation of the peritoneum in these 12 cases revealed 6 with acellular mucin alone, 3 with low-grade mucinous epithelium (all 3 with ovarian IM-LMP), and 3 with high-grade mucinous carcinomatosis (all 3 with ovarian mucinous adenocarcinoma). No appendiceal lesions were identified. Follow-up was available in 48% of patients (mean, 61 mo). The only adverse outcomes occurred in the 3 patients with ovarian carcinoma and associated peritoneal carcinomatosis. We report that a significant proportion of mucinous tumors associated with mature ovarian teratomas present with clinical PMP, which in most cases is associated with IM-LMP. PMP in this setting may harbor microscopic intra-abdominal low-grade mucinous epithelium that is histologically and immunophenotypically similar to that typically seen in appendiceal-related PMP. Pseudomyxoma ovarii is common in this setting, particularly in tumors with IM-LMP histology, but pseudomyxoma ovarii is not predictive of PMP. Ovarian teratoma-associated benign and IM-LMP mucinous neoplasms wi...

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Immunohistochemical expressions of cytokeratins, mucin core proteins, p53, and neuroendocrine cell markers in epithelial neoplasm of appendix

Cited by 22 publications

References 21 publications

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Differential protein immunoexpression profiles in appendiceal mucinous neoplasms: a special reference to classification and predictive factors

Ovarian Mature Teratomas With Mucinous Epithelial Neoplasms: Morphologic Heterogeneity and Association With Pseudomyxoma Peritonei

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