Clinical significance of MUC1, MUC2 and CK17 expression patterns for diagnosis of pancreatobiliary arcinoma

Yang, Haiyan; Tamayo, Rafael Ríos; Almonte, Maribel; Horten, Bruce; DaSilva, M; Gangi, Maryann D.; Vazquez, Ekie; Joseph, Dimitri; Okamoto, Patricia M.; Scholl, Thomas

doi:10.3109/10520295.2011.570276

Cited by 14 publications

(16 citation statements)

References 15 publications

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“…CK17 is a low-molecular-weight keratin that is normally expressed in myoepithelial and basal cells and subsets of hair shaft epithelia [13]. A few studies have demonstrated it to be of value in the distinction between pancreaticobiliary and nonpancreaticobiliary adenocarcinomas [13,16,30,31]. In accordance with published results, our data showed frequent CK17 expression in PDAs, seen in 60% of the cases.…”

Section: Discussionsupporting

confidence: 90%

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

et al. 2014

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Summary Distinction between primary intrahepatic cholangiocarcinoma (ICC) and metastatic pancreatic ductal adenocarcinoma (PDA) on a liver biopsy is essentially impossible histologically but has important clinical implications. In this study, 41 ICCs and 60 PDAs were immunohistochemically evaluated for the expression of S100P, pVHL, IMP3, maspin, MUC5AC, and CK17 proteins. The results showed pVHL expression in 29 (71%) ICCs but in only 3 (5%) PDAs. S100P, MUC5AC, and CK17 were frequently expressed in PDAs, seen in 57 (95%), 40 (67%), and 36 (60%) cases, respectively. In contrast, only 11 (27%), 5 (12%), and 5 (12%) ICC cases expressed these proteins. IMP3 was expressed in 37 (90%) ICC and 54 (90%) PDA cases with equal frequency. All 60 (100%) PDA and 30 (73%) ICC cases showed positive maspin immunoreactivity. A S100P−/pVHL+/MUC5A C−/CK17− staining pattern was essentially indicative of ICC, whereas the S100P+/pVHL−/MUC5AC+/ CK17+ and S100P+/pVHL−/MUC5AC−/CK17+ staining patterns were suggestive of PDA. These observations demonstrate that S100P, pVHL, MUC5AC, and CK17 are a useful immunohistochemical panel that may help distinguish primary ICC from metastatic PDA.

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Section: Discussionsupporting

confidence: 90%

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

et al. 2014

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“…In addition, we determined that K17 status is as a better negative prognostic marker than p27 KIP1 and tumor stage. We previously identified K17 as a candidate cervical cancer biomarker by proteomic analysis of normal cervical mucosa, cervical intraepithelial neoplasia, and cervical squamous cell carcinoma, and other reports have suggested that K17 expression may be overexpressed in pancreatic, urothelial, colorectal, and head and neck carcinomas (5,(36)(37)(38). Thus, these prior observations, together with our current in vitro and in vivo data, suggest that K17 expression could in fact be involved in oncogenic signaling of a wide range of cancer types.…”

Section: Discussionmentioning

confidence: 99%

“…Keratin 17 (K17), although not present in normal mature epithelia, is expressed in stem cells of embryonic ectoderm, skin appendages, and the endocervical mucosa, and it is re-expressed in carcinomas (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Keratin-17 Promotes p27KIP1 Nuclear Export and Degradation and Offers Potential Prognostic Utility

et al. 2015

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Keratins that are overexpressed selectively in human carcinomas may offer diagnostic and prognostic utility. In this study, we show that high expression of keratin-17 (K17) predicts poor outcome in patients with cervical cancer, at early or late stages of disease, surpassing in accuracy either tumor staging or loss of p27 KIP1 as a negative prognostic marker in this setting. We investigated the mechanistic basis for the biologic impact of K17 through loss-and gain-of-function experiments in human cervix, breast, and pancreatic cancer cells. Specifically, we determined that K17 functions as an oncoprotein by regulating the subcellular localization and degradation of p27 KIP1 . We found that K17 was released from intermediate filaments and translocated into the nucleus via a nuclear localization signal (NLS), specific among keratins, where it bound p27 KIP1 during G 1 phase of the cell cycle. p27 KIP1 lacks a nuclear export signal (NES) and requires an adaptor for CRM1 binding for nuclear export. In K17, we defined and validated a leucine-rich NES that mediated CRM1 binding for export. Cervical cancer cells expressing K17 mutations in its NLS or NES signals exhibited an increase in levels of nuclear p27 KIP1 , whereas cells expressing wild-type K17 exhibited a depletion in total endogenous p27 KIP1 . In clinical specimens of cervical cancer, we confirmed that the expressions of K17 and p27 KIP1 were inversely correlated, both across tumors and within individual tumors. Overall, our findings establish that K17 functions specially among keratins as an oncoprotein by controlling the ability of p27 KIP1 to influence cervical cancer pathogenesis. Cancer Res; 75(17); 3650-62. Ó2015 AACR.

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“…Evidence suggests that MUC expression is involved in the invasion and metastasis of various malignancies, including gallbladder cancer [19], breast cancer [20], ovarian cancer [21], gastric carcinoma [22,23], pancreatic carcinoma [24][25][26], ampullary cancer [27,28], lung cancer [16,29], prostate cancer [30], renal cell carcinoma [31], and appendiceal carcinoma [32]. However, the prognostic value of MUC expression in CRC remains controversial [33][34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

Zuo

Liu

et al. 2019

Gastroenterology Research and Practice

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Objective. To assess the association between MUC expression levels in colorectal cancer (CRC) tissues and prognosis and investigate the associations between MUC expression levels and CRC clinicopathological characteristics. Methods. The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception through September 13, 2019, to identify studies investigating the association between MUC expression levels in CRC tissues and prognosis. Pooled hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CIs) were used to evaluate associations between MUC expression levels and prognosis or clinicopathological characteristics, respectively. The heterogeneity between studies was assessed by the I2 values, whereas the likelihood of publication bias was assessed by Egger’s linear regression and Begg’s rank correlation test. Results. Among 33 included studies (n=6032 patients), there were no associations between combined MUC phenotype expression levels and overall survival (OS) or disease-free survival (DFS)/relapse-free survival (RFS) in patients with CRC. In subgroup analyses, the upregulated MUC1 expression (HR=1.50; 95% CI, 1.29–1.74; P<0.00001) was associated with poor OS. However, the upregulated MUC2 expression (HR=0.64; 95% CI, 0.52–0.79; P<0.00001) was associated with better OS. Furthermore, a high level of MUC1 expression (HR=1.99; 95% CI, 0.99–3.99; P=0.05) was associated with shorter DFS/RFS. However, patients with a low level of MUC2 tumors showed better DFS/RFS than patients with a high level of MUC2 tumors (HR=0.71; 95% CI, 0.49–1.04; P=0.08; P=0.0.009, I2=67%) and MUC5AC expression (HR=0.56; 95% CI, 0.38–0.82; P=0.003) was associated with longer DFS/RFS. In addition, a high level of MUC1 expression was associated with CRC in the rectum, deeper invasion, lymph node metastasis, distant metastasis, advanced tumor stage, and lymphatic invasion. A high level of MUC2 expression had a protective effect. High secretion of MUC5AC is associated with colon cancer compared with rectal cancer. Conclusion. The protein expression of MUC1 might be a poor biomarker in colorectal cancer and might play a role in tumor transformation and metastasis. However, the protein expression of MUC2 expression might have a protective effect. Furthermore, randomized controlled trials (RCTs) of large patients are needed to confirm the results.

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Clinical significance of MUC1, MUC2 and CK17 expression patterns for diagnosis of pancreatobiliary arcinoma

Cited by 14 publications

References 15 publications

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma

Keratin-17 Promotes p27KIP1 Nuclear Export and Degradation and Offers Potential Prognostic Utility

Prognostic and Clinicopathological Significance of MUC Family Members in Colorectal Cancer: A Systematic Review and Meta-Analysis

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