Main Session
Sep 30
QP 07 - GYN 3: Quick Pitch: Molecular Predictors of Outcomes in Cervical Cancer

1040 - Expression of Apoptotic Markers in Carcinoma Cervix Patients Undergoing Chemoradiotherapy

08:20am - 08:25am PT
Room 159

Presenter(s)

Satyajit Pradhan, MD Headshot
Satyajit Pradhan, MD - Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Varanasi, Uttar Pradesh

S. Pradhan1,2, S. Pal3, G. Narayan4, R. Ranjan3,5, and T. Singla1,2; 1Mahamana Pandit Madan Mohan Malaviya Cancer Centre, Varanasi, India, 2Homi Bhabha National Institute, Mumbai, India, 3Department of Radiotherapy & Radiation Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India, 4Department of Molecular & Human Genetics, Banaras Hindu University, Varanasi-221005, India, 5Kalyan Singh Superspecialty State Cancer Institute, Lucknow, India

Purpose/Objective(s): Tumorigenesis and progression correlate with genes associated with apoptosis and studies have shown relation and expression of apoptotic markers in cancer cervix. Family of Bcl-2 related proteins represent one of biologically relevant classes of apoptosis regulatory gene products, both death antagonist and agonist. Survivin is a member of the anti-apoptosis gene family. Aim of the present study was to: (i) Explore pre-treatment expression of Bcl-2 and Survivin and (ii) Correlate expression with patient characteristics and response to treatment in carcinoma cervix patients undergoing concurrent chemoradiation.

Materials/Methods: The present prospective study involved 36 histopathologically proven cancer cervix patients meeting the inclusion and exclusion criteria. All patients received chemoradiation that involved external beam radiation along with weekly Cisplatin 40mg/m2 and HDR brachytherapy. Tissue biopsy done before treatment was used for histological and immunohistochemistry examination for studying expression of Bcl-2 and Survivin.Immunoreactivity of Bcl-2 was observed in cytoplasm and of Survivin in both cytoplasm and nucleus. Grading of expression of Bcl-2 and Survivin was done as 1+, 2+, and 3+ depending on percentage of cells staining. Pre-treatment expression of these markers, were correlated with: patient age, disease stage, histology, tumor grade, tumor size, parametrial invasion, vaginal involvement, lymph nodal metastasis, and response to treatment.

Results: IHC staining in the 36 pretreatment biopsies showed Bcl-2 and Survivin positivity in 33(91.7%) and 34 (94.4%) samples, respectively. With respect to Bcl-2 , 1+, 2+ and 3+ positivity was seen in 18(50%), 11(30.6%) and 4(11.1%) samples, respectively. For Survivin, 1+, 2+ and 3+ positivity was seen in 20(55.6%), 9(25%) and 5(13.9%) samples, respectively. Stronger pre-treatment Bcl-2 expression was seen in patients having, (a) Advanced stage (p< 0.05), (b) Squamous cell histology (p<0.05), (c) Age group more than 50 yrs (p<0.05). Similarly for Survivin, stronger pre-treatment expression was seen in patients with (a) Advanced stage (p<0.05), (b) Squamous cell histology (p<0.05), (c) Higher grade of tumour (p<0.05). Most of the patients with low pre-treatment expression of Bcl-2 and Survivin had better response to treatment.

Conclusion: The study suggests that expression of Bcl-2 and Survivin was related to certain patient characteristics. Patients having decreased pretreatment expression of Bcl-2 and Survivin in terms of low positivity on IHC had better response to treatment. Hence, low expression of these markers in tumor samples could be a possible marker for response to radiation and overall treatment outcome.