Coordinate expression of cytokeratin 8 and cytokeratin 17 immunohistochemical staining in cervical intraepithelial neoplasia and cervical squamous cell carcinoma: An immunohistochemical analysis and review of the literature

Ikeda, Kota; Tate, Genshu; Suzuki, Takao; Mitsuya, Toshiyuki

doi:10.1016/j.ygyno.2007.11.042

Cited by 61 publications

(55 citation statements)

References 14 publications

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“…On the other hand, CK expression levels are reported to change dynamically with carcinogenesis, at least in some cases. Such changes include loss of CK7 and acquisition of CK20 in colorectal carcinoma (Park et al, 2002), acquisition of CK7 and loss of CK20 in gastric carcinoma (Park et al, 2002;Kim et al, 2004), or acquisition of CK 1, 5, 6, 8, 19 in squamous cell carcinoma (Xu et al, 1995;Chu and Weiss, 2002b;Ikeda et al, 2008). Furthermore, these changes correlated with malignant transformation or metastatic ability and were associated with poor prognosis (Kim et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from CK8/18, earlier reports described loss of CK7 and acquisition of CK20 in colorectal carcinoma (Park et al, 2002), acquisition of CK7, and loss of CK20 in gastric carcinoma (Park et al, 2002;Kim et al, 2004), and acquisition of CK1,5,6,8,19 in squamous cell carcinoma (Xu et al, 1995;Chu and Weiss, 2002a, b;Ikeda et al, 2008). Thus, it seems that CK expression in epithelial tissues can change with differentiation or malignant transformation in an organ-specific manner (Kurokawa et al, 2006).…”

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confidence: 99%

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Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

et al. 2009

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BACKGROUND: Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression. METHODS: We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis. RESULTS: Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (Po0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P ¼ 0.020), pN number (P ¼ 0.001), and CK18 expression (P ¼ 0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P ¼ 0.045). CONCLUSION: CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

et al. 2009

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“…This result probably represents the highest limit as compared to the findings of others. Intensive parabasal staining for p16 antigen was described in not more than 47% of CIN I cases, but continuous positive staining of lower intensity was reported in over 70% of CIN I cases [40,41]. Summing up the results of antigen p16 staining in the biopsy sections graded CIN I/LSIL, Yildiz et al [42] recognized continuous parabasal staining of high intensity, continuous parabasal staining of lower intensity and scattered staining of dispersed squamous epithelium cells.…”

Section: Overexpression Of the P16/ink4a Polypeptide In Hpv Transformmentioning

confidence: 99%

Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

Rajčáni¹,

Adamkov²,

et al. 2010

Open Life Sciences

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Abstract:The p16/INK4A protein is a cellular regulatory polypeptide over-expressed in the presence of high levels of the Human Papillomavirus (HPV) coded E7 protein. This review outlines the use of p16 antigen staining in cervical biopsies as well as in PAP smears summarizing the corresponding literature and commenting the authors' own experience. The p16 antigen is a reliable marker for dysplastic cells in CINII/CINIII (HSIL) lesions as viewed in cervical biopsies. When PAP smears were examined at large scale screening for p16 antigenreactive and atypical cells, considerable variations could be found especially in ASCUS graded lesions. Therefore, the presence of p16-reactive atypical cells in PAP smears should be interpreted together with the cytological signs of dysplasia, such as the altered N/C ratio. In addition, women revealing p16-positive ASCUS/LSIL specimens should be examined for the presence of HPV DNA. Detection of HPV DNA alone, i.e. in the absence of cytological screening has a low predictive value, since the clearance of HPV may occur even in the absence of morphological alterations. Combined cytological as well as molecular follow up contributes to the efficiency of diagnostic and increases the probability of correct interpretation of the pre-cancerous lesions by non-invasive techniques.

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“…Therefore, only K14 and K19 were tested in the present study, and strong cytoplasmic immunostaining for K14 and K19 was obtained in the majority of high-grade CIN keratinocytes. Additionally, P63 and K17 are specific markers of cervical stem cells (22)(23)(24), and staining of the markers was detected in the majority of the cultured CIN cells. In addition, the passaged keratinocytes remained HPV-positive; therefore, the CIN keratinocytes cultured in the present study were considered to originate from cervical stem cells, and did not change from the original characteristics in the in vitro culture.…”

Section: Discussionmentioning

confidence: 98%

A modified method for the culture of naturally HPV-infected high-grade cervical intraepithelial neoplasia keratinocytes from human neoplastic cervical biopsies

2016

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Abstract. Few studies on cervical intraepithelial neoplasia (CIN) keratinocyte cultures are available due to the numerous technical and methodological problems associated with the in vitro cultivation of these cells. The present study investigated an applicable and effective method for the in vitro cultivation of high-grade CIN keratinocytes from human neoplastic cervical biopsies. Human neoplastic cervical tissue sections were obtained and digested using type I collagen in order to dissociate the cells. The cells were seeded in tissue culture plastic plates that were coated with rat tail collagen type I and contained modified keratinocyte serum-free medium (K-SFM) supplemented with 5% fetal bovine serum. The medium was replaced with K-SFM on days 3, 5 and 7, respectively. The unattached cells were recovered and the cell viability was determined accurately using the Trypan Blue exclusion method. The expression of keratin 14 (K14), keratin 19 (K19), keratin 17 (K17) and P63 was assayed using immunofluorescence in order to identify the presence of CIN keratinocytes. The present results indicated that the attachment rate of CIN keratinocytes significantly increased between 56.75±1.76% on day 3 and 77.09±3.55% on day 5, and became relatively stable between days 5 and 7. The cell viability significantly decreased between 83.00±0.50% on day 5 and 68.17±1.04% on day 7. The passaged CIN keratinocytes maintained the original unequally sized, abnormally shaped morphology and did not undergo differentiation. In addition, the passaged CIN keratinocytes exhibited the same human papilloma virus (HPV) genotype that was detected in the original primary cells. K14 and K19 were expressed in the majority of the normal and CIN keratinocytes, whereas K17 and P63 were expressed only in high-grade CIN keratinocytes. The present study proposes a simple and practical method for rapidly obtaining highly purified naturally HPV-infected high-grade CIN keratinocytes from small neoplastic cervical tissues, and provides an appropriate first medium change time for the primary culture of CIN keratinocytes. IntroductionCervical cancer is the most common gynecological cancer worldwide and is usually preceded by a long phase of pre-malignant disease (1,2). These pre-malignant changes represent a spectrum of histological abnormalities ranging between cervical intraepithelial neoplasia (CIN) I (mild dysplasia), CIN II (moderate dysplasia) and CIN III (severe dysplasia/carcinoma in situ) (3,4). In the majority of patients, CIN I will regress spontaneously and is not usually precancerous; however, 20-45% of untreated CIN II and III lesions will persist and progress to cervical cancer (5,6). Therefore, CIN II and CIN III are considered to be high-grade precancerous lesions. Previous studies have established that the majority of high-grade CIN cases are caused by persistent oncogenic human papilloma virus (HPV) infection, and a long latency period of viral infection is required for CIN progression (7-9). However, viruses do not metabolize, and require a...

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Coordinate expression of cytokeratin 8 and cytokeratin 17 immunohistochemical staining in cervical intraepithelial neoplasia and cervical squamous cell carcinoma: An immunohistochemical analysis and review of the literature

Cited by 61 publications

References 14 publications

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

Diagnostic role of p16/INK4A protein in Human Papillomavirus (HPV) induced cervical dysplasia

A modified method for the culture of naturally HPV-infected high-grade cervical intraepithelial neoplasia keratinocytes from human neoplastic cervical biopsies

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