A Study of Cytokeratin-7 Expression and Clinicopathological Correlation in Dysplasia and Squamous Cell Carcinoma of the Cervix

Abstract

Objectives: Cytokeratin (CK) proteins play a vital role in cancer diagnosis, of which,CK-7 is a prominent marker of squamocolumnar junction cells corresponding to the the initiating site of cervical cancer.The current study is aimed to evaluate the expression pattern of CK-7 and to corelate with the clinicopathological features in patients with cervical dysplasia and invasive squamous cell carcinoma.

Methodology: The hysterectomy and biopsy specimens from women with cervical dysplasia (n=60) and carcinoma (n=60) were evaluated histopathologically and processed for immunohistochemistry (IHC) staining to assess for CK-7 expression. The relationship between CK-7 expression and tumor characteristics like histological type of cervical intraepithelial neoplasia (CIN), tumor type and grade was evaluated. Data was analyzed using the Chi-square test ,wherein the p value ≤ 0.05 were taken for statistical significance.

Results: Positive CK-7 expression was observed in 25 (41.67%) dysplasia and in 34 (56.67%) carcinoma cases. Majority of the cases were CIN III (n=31, 51.67%), large cell non-keratinizing tumor type (n=54, 90%) and moderately differentiated grade of tumor (n=52, 86.67%), out of which 18 (58.1%), 34 (62.96%) and 30 (57.69%) cases were CK-7 positive, respectively. The difference in clinical diagnosis and tumor characteristics over CK-7 expression was significant (p<0.05). The pattern of CK-7 expression in dysplasia and carcinoma cases were diffuse in 23 (38.33%) and 31 (51.67%) respectively and patchy in 2 (3.33%) and 3 (5%) of them, respectively.

Conclusion: Significant positive CK-7 expression in cervical dysplasia and carcinoma indicates a good clinical course and its role as a useful predictable marker for cancer progression.

Keywords: Keratins; Squamous Cell Carcinoma; cervical intraepithelial neoplasia; immunohistochemistry.

Figure 1

(A) Gross image of hysterectomy specimen showing grey-white infiltrating tumor in the cervix, (B) hysterectomy specimen showing grey-white exophytic growth at the posterior lip of the cervix and (C) cone biopsy specimen of the cervix showing grey-white and hemorrhagic areas of CIN III

Figure 2

(A) H&E staining of CIN I under 10X, (B) IHC staining of CIN I - dysplastic epithelium showing negative CK-7 expression under 10X, (C) H&E staining of CIN II under 10X, (D) IHC staining of CIN II – superficial epithelial cells showing positive CK-7 expression under 10X, (E) H&E staining of CIN III under 10X and (F) IHC staining of CIN III - dysplastic epithelium showing positive CK-7 expression under 10X

Figure 3

(A) H&E staining of squamous cell carcinoma under 20X, (B) IHC staining of squamous cell carcinoma showing diffuse membranous and cytoplasmic positivity of CK-7 expression under 20X (C) H&E staining of poorly differentiated carcinoma under 20X, (D) IHC staining of poorly differentiated carcinoma under 20X showing tumor cells negative for CK-7 expression under 20X and (E) positive internal control – endocervical glands showing diffuse membranous positive CK-7 expression under 100X