With the progress in diagnostic molecular pathology, a comprehensive evaluation system including the expression of metastasis-related proteins should be used to guide clinical treatment and predict prognosis. Junko Sakurada, Email: pj.og.nhs@20arukas. Single stromal PGCCs with budding were also observed in CRCs [12].

2()). Note that normal crypt architecture is seen on the left side of the picture (red arrows) (original magnification 100). Annals of surgery. Adenocarcinoma of the cervix accounts for 7 to 22% of cervical malignancies [6]. 3b). 3A-b and -e). PloS one. For the CK7 positive group, diffuse or focal CK7 positive tumor cells were present in tumor tissue. Finally, the cells were counterstained with hematoxylin and examined under a microscope. The clinical staging of CRC is mainly based on the invasive depth of tumor cells and the presence of metastasis. Distinct cytoplasmic immunoreactivity of CK7 was considered positive. 2018;20:794-800, 14. Muc-2 IHC staining results were negative for these adenocarcinomas and the tumor foci were single. 2B-c and -d), and lymph node metastases (Fig. 2012;51:411-21, 19. The number of PGCCs was associated with cancer development, metastasis, chemoresistance, and progression, and there were more PGCCs in cancers of high pathological grades, late stage diseases, recurrent tumors, and after chemotherapy. Molecular carcinogenesis. PGCCs were often located at the invasion front, which is the boundary of tumor infiltration into normal tissue. reported that CK7 expression related with the status of BRAF and microsatellite stability and there was more expression of CK7 in BRAF-mutated microsatellite stable (MSS) colorectal carcinoma compared to both BRAF-mutated high-level microsatellite instability (MSI-H) colorectal carcinoma and BRAF wild-type MSS colorectal carcinoma [47]. Understanding this association can help us to further explore the basis of tumor metastasis and patient prognosis. thismailbody12 = thismailbody12+thismailbody11; 1A-e and -f) CRCs could express CK7. Journal of gastroenterology and hepatology. (b) CK7 IHC staining of (a) (IHC, 10). Colposcopy revealed a tumorous lesion on the posterior fornix (Fig. Conclusion: CRC cells expressing CK7 may have strong invasive and metastatic abilities. We first reported that polyploid giant cancer cells (PGCCs) could be induced and purified by CoCl2 in vitro and confirmed that PGCCs had the properties of cancer stem cells [6]. Br J Cancer. var thismailbody1 = ""; 2009;60:207-19, 4. However, the percentage of well and moderately differentiated tumor was 80.37% (86 of 107) in CK7 negative CRCs. Note that a normal appendix is apparent. NO, JS, and HS performed the histopathological examinations and made the diagnosis. As described above, CK7 expression was associated with the location, differentiation, lymph node metastasis, and the Dukes' stage of CRCs. PGCCs and some daughter cells yielded positive ICC staining results for CK7 (Fig. Graham RP, Vierkant RA, Tillmans LS, Wang AH, Laird PW, Weisenberger DJ. Anticancer Res. Levels of carbohydrate antigen 125 and squamous cell carcinoma antigen were also within normal ranges. var thismailbody12 = "aliyu"; 2018, 3. 2011;59:225-34, 17. Tumor budding may have the same origin as the micropapillary pattern, and they may both be derived from PGCCs and their budding daughter cells, which show strong invasive abilities. Bauer KM, Hummon AB, Buechler S. Right-side and left-side colon cancer follow different pathways to relapse. 1B-g and -h). James R, Kazenwadel J. Homeobox gene expression in the intestinal epithelium of adult mice. 3B-c and -f). Some metastasis-related morphological characteristics in CRCs including the invasion front, micropapillary pattern, tumor emboli, and single stromal PGCCs associated with CK7 positive expression. We searched the database at the Department of Pathology for cases of CRC. All authors read and approved the final manuscript. Received 2015 Aug 6; Accepted 2016 Jan 11. Lemoine NR, Hall PA. Epithelial tumors metastatic to the uterine cervix. var thismailbody11 = ""; A 74-year-old postmenopausal Japanese woman was referred to our hospital for the evaluation of a uterine tumor. The difference in tumor differentiation between CK7 positive and negative CRCs was statistically significant (2 = 7.339, P = 0.007). (e) PGCCs (black arrows) with their generated daughter cells (red arrows) (H&E, 10). PMC legacy view De Lott LB, Morrison C, Suster S, Cohn DE, Frankel WL. 1999;81:709-15, 10. reported that high-grade ovarian carcinoma had more single stromal PGCCs than low-grade ovarian carcinoma [23, 24]. Clinicopathological and molecular characterization of colorectal micropapillary carcinoma. Zhang S, Mercado-Uribe I, Xing Z, Sun B, Kuang J, Liu J. CK7 was localized in the cytoplasm of PGCCs and their daughter cells. Next, we evaluated the significance between single stromal PGCCs and CK7 IHC staining in CRCs.

Tumor cells positive for at least 3 of these 4 proteins were regarded as originating from the colorectum. It is reported that CK7 was positive associated with ulcerative colitis (UC)-associated neoplasms [44]. A new prognostic staging system for rectal cancer. In our case, the immunohistochemistry of our patients cervical biopsy and surgical specimen showed a CK7-positive/CK20-negative expression pattern (Fig.

The .gov means its official. International journal of cancer Journal international du cancer. McCluggage WG, Hurrell DP, Kennedy K. Metastatic carcinomas in the cervix mimicking primary cervical adenocarcinoma and adenocarcinoma in situ: report of a series of cases. In well and moderately differentiated CRCs, the distribution of CK7 positive cells was not uniform and was mainly at the edge of cancer nests, the invasion front, tumor buds [16], single stromal PGCCs, intravascular tumor emboli, and cells growing in a micropapillary pattern. reported that all cervical adenocarcinoma and adenocarcinoma in situ samples (38/38) were diffusely positive for CK7 [11]. Results of immunocytochemical (ICC) staining and western blot showed that the level of cytokeratin 7 (CK7) expression increased after CoCl2 treatment. Scattered PGCCs were observed in control LoVo and HCT116 before CoCl2 treatment. Tel: (086)13652136865; Fax: (86)022-87721989. (g) H&E staining of poorly differentiated CRC (H&E, 10). 2013;42:525-9, 18. Western blot analysis confirmed that CK7 expression was increased in PGCCs and their budding daughter cells compared to control LoVo and HCT116 (Fig. Polyploid giant cancer cells with budding and the expression of cyclin E, S-phase kinase-associated protein 2, stathmin associated with the grading and metastasis in serous ovarian tumor. HHS Vulnerability Disclosure, Help Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc. 2015;28:1584-93, 46. Nankai University School of Medicine, Nankai University, Tianjin, P.R. Metaplasia, intraepithelial neoplasia and early cancer of the stomach are related to dedifferentiated epithelial cells defined by cytokeratin-7 expression in gastritis. Arch Pathol Lab Med. (c) Cells growing in a micropapillary pattern in CRCs (H&E, 10). 2004;240:832-9, 42. Am J Surg Pathol. Werling RW, Yaziji H, Bacchi CE, Gown AM. Gastroenterology research. Nakagami K, Takahashi T, Sugitani K, Sasaki T, Ohwada S, Morishita Y. The primary antibody used was CK7, with -actin (Sigma-Aldrich) used as a control.

The authors thank Dr. Atsushi Koyama (Sendai Open Hospital, Sendai, Japan) for providing the medical information. c Pelvic magnetic resonance image of a T2-enhanced sagittal section showing an irregularly enlarged uterine cervical tumor (red arrow). (e) H&E staining of well differentiated CRC with scattered distribution of single cancer cells (H&E, 10). var thismailbody11 = ""; thismailbody3 = thismailbody1; var thismailbody2 = ""; Furthermore, both CA19-9 and CEA rapidly returned to levels within normal limits after the patient underwent radical hysterectomy (Fig. Cytoplasmic immunoreactions for CK7, CK20, villin and cadherin 17 IHC staining were considered as positive and CDX2 IHC staining showed dense positive brown nuclear immunoreactions. However, performing a histopathological diagnosis that discriminates between a colorectal adenocarcinoma metastatic to the cervix and a primary cervical adenocarcinoma with colonic differentiation is difficult [9]. Cytokeratin 7/20 and mucin core protein expression in ulcerative colitis-associated colorectal neoplasms. After washing with PBS, these slides were incubated overnight with mouse anti-CK7 (MXB Biotechnologies Inc., Fuzhou, China, Kit-0021, 1:100 dilution) at 4C. Sullivan LM, Smolkin ME, Frierson HF, Galgano MT. Internal and digital examinations were negative for parametrial and rectal involvement. ICC and western blotting also confirmed that LoVo and HCT116 PGCCs and their daughter cells had higher CK7 expression than the control cells. Department of Pathology, Tianjin Union Medical Center, Tianjin, P.R. Zhang S, Mercado-Uribe I, Hanash S, Liu J. iTRAQ-based proteomic analysis of polyploid giant cancer cells and budding progeny cells reveals several distinct pathways for ovarian cancer development. We previously reported that PGCCs induced by CoCl2 could generate daughter cells with strong migratory and invasive abilities. Comprehensive evaluation of CDX2 in invasive cervical adenocarcinomas: immunopositivity in the absence of overt colorectal morphology. 1B-a and -b) and the invasion front (Fig. However, CDX2 expression may also be positive in adenocarcinomas of the upper gastrointestinal tract and other lesions, including those of the uterine cervix. Zhang S, Mercado-Uribe I, Sood A, Bast RC, Liu J. Coevolution of neoplastic epithelial cells and multilineage stroma via polyploid giant cells during immortalization and transformation of mullerian epithelial cells. (d) CK7 positive staining of (c) (IHC, 10). Furthermore, hyperplastic polyps and serrated adenoma in the colorectum yielded positive staining results for CK7 and canalicular adenoma yielded negative results for CK20. 1. The Journal of cell biology. 2007;16(Suppl 1):S7-9, 47. (b) Few PGCCs from LoVo (black arrows) yielded positive IHC staining results for CK7 before CoCl2 treatment (IHC, 10). CK7 positive cells were not uniformly distributed and mainly were distributed at the edge of cancer nests, the invasion front, tumor buds, as single stromal PGCCs, in intravascular tumor emboli, and in the micropapillary pattern. Tumor budding and the micropapillary pattern may both be derived from PGCCs and their budding daughter cells [7]. CDX2, Cecal cancer, Cervical metastasis, Cytokeratin 7, Cytokeratin 20, Immunohistochemistry, Tumor marker. 2A-f). CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. 1A-c and -d), and poorly differentiated (Fig. After CoCl2 treatment, the PGCCs and their daughter cells of LoVo and HCT116 yielded positive results in CK7 ICC staining. Jass JR. Molecular heterogeneity of colorectal cancer: Implications for cancer control. Kirchner T, Muller S, Hattori T, Mukaisyo K, Papadopoulos T, Brabletz T. et al. The Institutional Review Board of Tianjin Union Medical Center approved this study, and patient anonymity was maintained. The evidence from our rare case was consistent with a metastasis to the uterine cervix that originated from a distant tumor. Zhang D, Yang X, Yang Z, Fei F, Li S, Qu J. et al. 3A-c and -f). 2015;31:219-22, 26. Onco Targets Ther. PGCCs in CRC (H&E, 10). Virchows Archiv: an international journal of pathology. It has been reported to appear in cancers of the breast, bladder, lung, pancreas, ovary, urothelial tract, and stomach [26-29] and is associated with tumor differentiation, lymph node and distant metastasis, and lymphovascular tumor emboli [7, 17]. (b) LoVo PGCCs survived the treatment of 300 M CoCl2 for 48 h (black arrows, 10). 4d), p16, estrogen receptor, progesterone receptor, vimentin, calretinin, and cluster of differentiation-10 expression. After recovery from CoCl2 treatment, PGCCs could generate daughter cells via budding (Fig. (d) Morphological characteristics of HCT116 cells before CoCl2 treatment (10). CK7 positive CRCs from more than one thousand cases in our hospital were used to study the clinicopathological significance and 107 cases of CK7 negative CRCs were used as a randomized controlled comparison. 2018;11:264-73, 20. The diffuse distribution of CK7 positive tumor cells was often present in poorly differentiated CRCs. a cancer journal for clinicians. Verdu M, Roman R, Calvo M, Rodon N, Garcia B, Gonzalez M. et al. Dukes CE, Bussey HJ. In pathology, PGCCs were the key contributors to cellular atypia and were associated with the malignant grade of tumors. Primary cancers of the cecum are anatomically less likely to invade the uterine cervix than primary rectosigmoid cancers. Tumor cell morphology at the invasion front is different from that in the tumor center. BMC cancer. In poorly differentiated CRCs, almost all tumor cells were CK7 positive (Fig. 2014;14:576, 21. com. The patient is currently receiving adjuvant chemotherapy and to date is without evidence of recurrent disease.