Alterations found in pl6/Rb/cyclin D1 pathway in the dysplastic and malignant cervical epithelium.

Cervical cancer is the one of the most common cancers affecting the south Indian women. The objective of the present study was to analyze the pl6/Rb/cyclin D1 pathway in the normal (n=30), dysplastic (n=56), and malignant cervical epithelium (n=142) using immunohistochemistry. The positive immunoreactivity for p16 was as follows: CIN I--1/12 (8.3%), CIN II--2/8 (25%), CIN III--31/36 (86.1%), and in invasive tumors-121/142 (85.1%); for cyclin D1 it was CIN I--4/12 (66.6%), CIN II--5/8 (62.5%), CIN III--0%, and invasive tumors--5/142 (3.5%); and for pRb it was CIN I--9/12 (75%), CIN II--5/8(62.5%), CIN III--1/36 (97.2%), and in invasive tumors--41/142 (28.8%). Expression of cyclin D1 and p16 in the CINs were mutually exclusive and the correlation between the two biomarkers was found to be statistically significant (p = 0.0009). There was downregulation of pRb in invasive cancers, with only 32% (39/121) of the p16-positive tumors being positive for pRb (p = 0.032). Analysis of the pattern of expression of these biomolecules showed increased p16-positive phenotypes and decreased cyclin D1- and pRB-positive phenotype among the invasive tumors compared to low-grade CIN lesions.

CDC27 protein is involved in radiation response in squamous cell cervix carcinoma.

In the present study, an attempt was made to identify genes involved in radiation response in cervix carcinoma. Differential display technique was used to study the expression profiles of tumour biopsy samples obtained from patients, responding and not responding to treatment. The samples were obtained prior to radiotherapy and subsequent to treatment with Tele-radiation at 10 Gray (Gy). One of the differentially expressed cDNAs, when sequenced was identified to be CDC27. Immuno-histochemical analysis of pre- and post-treated tumour samples from fifteen patients showed the downregulation of expression of CDC27 protein in seven patients. Down-regulation was associated with poorer response to radiotherapy. Cervical cancer cell lines SiHa and C33A were irradiated and their nuclei were stained for expression of CDC27 and analyzed using fluorescent-activated cell sorting (FACS). Down-regulation of CDC27 protein in the irradiated SiHa cell line was associated with greater survival fraction, compared to the irradiated C33A cell line, which had only slight fall in the level of CDC27 protein. This is the first study to suggest a role for CDC27 in radiation response. However, a larger cohort is needed to further confirm the value of CDC27 protein as a predictive marker, for radiation response in cervix cancer.

C-myc oncoprotein expression and prognosis in patients with carcinoma of the cervix: an immunohistochemical study.

OBJECTIVE: Evaluation of the prognostic significance of c-Myc expression in carcinoma of the cervix. MATERIALS AND METHODS: 132 patients with carcinoma of the cervix presenting at the Cancer Institute in Chennai from 1996-1999 were included in the study. All the cases were treated with a radical course of radiotherapy and had a median follow-up of 36 months. Paraffin blocks obtained from the punch biopsies from the tumours were used for immunohistochemistry. RESULTS: c-Myc nuclear immunoreactivity was observed in 44/132 (33.3%) of tumours. Patients with tumours in Stages 11 B and III B accounted for 112/132 (84.8%) of the cases. Patients with tumours expressing c-Myc nuclear immunoreactivity were found to have more advanced disease; less likely to achieve complete remission (54.5% vs. 78.4%; p < 0.005) and lower disease-free status (52.3% versus 73.8%; p < 0.014). The poor prognostic feature of c-Myc nuclear immunoreactivity was seen in both stage II B (52.9% vs. 76.3%) and stage III B (38.1% vs. 69.4%; p < 0.025). CONCLUSIONS: c-Myc nuclear immunoreactivity is a predictor of poorer response to radiotherapy and poorer disease free status in stage II B and III B carcinoma of the cervix.

Prognostic significance of Bcl-2 and p53 protein expression in stage IIB and IIIB squamous cell carcinoma of the cervix.

Cervical cancer is the most common cancer among women in South India. More than 70% of the cases present in stage IIB and IIIB and of these more than 50% fail conventional treatment. The purpose of the present study was to determine the prognostic significance of Bcl-2 and p53 expression in squamous cell carcinomas of the cervix. Using immunohistochemistry, 40 cases of stage IIB and IIIB squamous cell carcinomas of the cervix treated with radiotherapy were studied for the expression of Bcl-2 and p53 protein and their prognostic value ascertained. Bcl-2 was expressed in 65% (n=26) of the tumours. There was a statistically significant association (p=<0.025) between Bcl-2 expression and poorer DFS and OS in stage IIB cases. In stage IIIB, these associations were not obvious probably due to additional genetic events overshadowing the significance of Bcl-2 expression. Only 4/40 (10%) of the cases were positive for p53 protein expression and there was an inverse correlation between p53 expression and Bcl-2 expression. This study suggests that Bcl-2 can be a useful marker to identify the poor prognostic group in stage IIB cases and needs to be confirmed in a larger series.