Aberrant cytokeratin expression as a possible prognostic predictor in poorly differentiated colorectal carcinoma

Yamagishi, Hidetsugu; Imai, Yasuo; Okamura, Takuya; Fukuda, Kazunori; Ono, Yuko; Ban, Shinichi; Inoue, Tohru; Ueda, Yoshihiko

doi:10.1111/jgh.12319

Cited by 22 publications

(19 citation statements)

References 29 publications

(59 reference statements)

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“…Yamagishi et al paid specific attention to CRCs with variant histology (i.e., poorly differentiated, mucinous, signet ring, etc.). The authors found a negative prognostic significance for CK20 expression in poorly differentiated carcinomas, while this association was not found in well/moderately differentiated CRCs or in CK7 18 . In concordance with our results, the authors showed increased CK20 expression in MMR proficient tumors, which is in line with previously published studies 8 , 14 , 15 .…”

Section: Discussionmentioning

confidence: 88%

“…Yamagishi et al used a cut-off value of 1% for CK7 and 25% for CK20. The authors argue that since normal colonic mucosa does not express CK7 and only show diffuse expression of CK 20, any CK7 expression should be considered abnormal even at 1%, and CK20 < 25% should be evaluated as abnormally downregulated 18 . The point concerning CK20 is reasonable from our point of view, but for CK7, we think that expression in < 10% of tumor cells barely represents a significant expression since we had some cases in which CK7 + staining was only present in single cells, which in the words of Harbaum et al could be a “freak of nature” 14 .…”

Section: Discussionmentioning

confidence: 99%

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Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Hrudka

Fišerová

Jelínková

et al. 2021

Sci Rep

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Colorectal carcinoma (CRC) is associated with significant morbidity and mortality worldwide. Cytokeratins (CKs) are widely expressed in various types of carcinomas, whereas in CRC it is usually CK7 − and CK20 + . A subset of CRCs is CK7 + . This study aims to determine the prevalence of CK7 expression in CRC and its impact on overall survival. We analyzed 300 randomly selected surgically treated CRC cases using paraffin embedded tumor tissue samples and evaluated CK7 and CK20 expression using the tissue microarray method. Tumors with positivity > 10% and > 25% of tumor cells were considered CK7 and CK20 positive, respectively. Expression of both CKs and several clinical-pathological variables (stage, grade, laterality, mismatch-repair/MMR status) were evaluated using patient follow up data (Kaplan–Meier analysis of cancer-specific survival (CSS)). Significant results include shorter CSS (restricted mean 4.98 vs. 7.74 years, P = 0.007) and 5-year survival (29.4% vs. 64.6%, P = 0.0221) in CK7 + tumors compared to CK7 − tumors, respectively; without significant association with grade, stage or right-sided location. These results were significant in a multivariate analysis. CK20 + tumors are more frequently MMR-proficient and left-sided. MMR-deficient tumors are more frequently right-sided and had longer survival. CK7 expression, right-sided location (rmean CSS 6.83 vs. 8.0 years, P = 0.043), MMR-proficiency (rmean CSS 7.41 vs. 9.32 years, P = 0.012), and UICC stages III + IV (rmean CSS 6.03 vs. 8.92 years, P < 0.001) of the tumor correlated with negative prognostic outcomes, whereas the most significant results concern stage and CK7 positivity. The result concerning negative prognostic role of CK7 differs from those obtained by several previous studies focused on this topic.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Hrudka

Fišerová

Jelínková

et al. 2021

Sci Rep

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“…Pulmonary Metastasectomy for mCRC in Brazil [34,35]. A possible explanation is that these observations were performed in localized instead of metastatic colorectal cancer, thus limiting generalizability of this finding to our sample.…”

Section: Discussionmentioning

confidence: 99%

Outcomes and Prognostic Factors of Patients with Metastatic Colorectal Cancer Who Underwent Pulmonary Metastasectomy with Curative Intent: A Brazilian Experience

et al. 2021

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Background. We aimed to identify clinicopathological and molecular features associated with progression-free survival (PFS) and overall survival (OS) after pulmonary metastasectomy for metastatic colorectal cancer in a retrospective cohort in Brazil. Materials and Methods. We did a retrospective review of thoracic surgeries performed in a single large academic hospital in Brazil from January 1985 to September 2019. Demographics, previously described prognostic factors, and clinicopathological and molecular characteristics were abstracted. Univariate Cox regression was performed for each variable, and, when significant, data were dichotomized to provide clinically meaningful thresholds. Results. Records from 698 patients were reviewed. Fiftyeight patients underwent pulmonary metastasectomy with curative intent. Of those, 53.4% had a single metastatic lesion. The median size of the largest lesion was 1.5 cm.Results of RAS, RAF, and mismatch repair testing and of cytokeratin 20 (CK20) and CDX2 testing were available for 13.8% and 58.6% of the sample, respectively. Median PFS was 14 months, median OS was 58 months, and 5-year survival was 49.8%. Unfavorable prognostic factors for OS included disease-free interval (DFI) <24 months, synchronous presentation, size of the largest lesion ≥2 cm, and loss of CK20 expression. Presenting with more than one lesion was prognostic for PFS but not for OS. Conclusion.In this Brazilian cohort, our findings corroborate existing data supporting DFI, synchronous presentation, and number and size of lesions as prognostic factors. Furthermore, we found that loss of CK20 expression may be associated with more aggressive disease and shorter OS. Additional molecular prognostic factors after pulmonary metastasectomy for colorectal cancer should be further explored. The Oncologist 2021;26:1-8Implications for Practice: This study consolidates disease-free interval, synchronous presentation, and number and size of lesions as clinically relevant data that may help guide therapy for patients with colorectal cancer and lung metastases who are candidates for curative-intent metastasectomy. Additionally, in this sample, lack of cytokeratin 20 expression in metastases was associated with shorter progression-free survival and overall survival, suggesting that biomarkers also may have a role in guiding therapy in this setting and that additional biomarkers should be further explored.

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“…CK7 is expressed in several simple ductal and glandular epithelia, including the lung, breast, bile and pancreatic ducts, urinary tracts, ovary and endometrium (27). In contrast, CK7 expression is generally lacking in normal mucosa of the colon, rectum and, correspondingly, in colorectal adenoma and adenocarcinoma (11,28).…”

Section: Discussionmentioning

confidence: 99%

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer

et al. 2017

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The multi-step progression of colorectal cancer through precancerous lesions (adenoma and dysplasia) is associated with cumulative molecular alterations, a number of which have also been demonstrated to be present in morphologically normal transitional mucosa adjacent to colorectal cancer. The cytoskeletal protein cytokeratin 7 (CK7) and the receptor tyrosine kinase, KIT proto-oncogene receptor tyrosine kinase (CD117), encoded by the proto-oncogene c-Kit, are lacking in normal colorectal crypt epithelium and are aberrantly expressed in a subset of colorectal cancer. The aim of the present study was to evaluate the expression of CK7 and CD117 in morphologically normal transitional mucosa adjacent to colorectal cancer. Immunohistochemical staining for CK7 and CD117 was performed in the mucosa adjacent to five groups of surgically resected colorectal tumors [low-grade adenoma, high-grade adenoma, mucosal adenocarcinoma, small-sized invasive adenocarcinoma (≤2 cm) and large-sized invasive adenocarcinoma (>2 cm)]. CK7 was expressed in the mucosa adjacent to a subset of colorectal tumors, and the positivity ratio increased according to tumor grade from low-grade adenoma up to small-sized invasive adenocarcinoma (61.2%). However, the positivity ratio of CK7 in the mucosa adjacent to the large-sized invasive adenocarcinoma (25.0%) was significantly lower compared with that of the next lower grade. CD117 was also expressed in the mucosa adjacent to a subset of colorectal tumors. In contrast to CK7, the positivity ratio of CD117 increased according to tumor grade from low-grade adenoma all the way through to the large-sized invasive adenocarcinoma (45.0%). Based on these results, the mechanism of CK7 and CD117 expression in the transitional mucosa adjacent to colorectal cancer may be different, and analysis of their individual expression may provide novel insights into the development and progression of colorectal cancer.

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Aberrant cytokeratin expression as a possible prognostic predictor in poorly differentiated colorectal carcinoma

Abstract: CK20 status may be used as a prognostic predictor of PDA.

Cited by 22 publications

References 29 publications

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Cytokeratin 7 expression as a predictor of an unfavorable prognosis in colorectal carcinoma

Outcomes and Prognostic Factors of Patients with Metastatic Colorectal Cancer Who Underwent Pulmonary Metastasectomy with Curative Intent: A Brazilian Experience

Altered expression of cytokeratin 7 and CD117 in transitional mucosa adjacent to human colorectal cancer

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