STAT3 and the Immune Response in CIN and Invasive Squamous Cell Carcinoma
Alyaa Al-Ibraheemi, Xuizhen Duan, Ronny Zhang, Robert E Brown. UT Health Medical School, Houston, TX
Background: The STAT3 pathway has been shown to be activated in HPV-associated pathology of the uterine cervix. Because STAT3 is transcriptionallyinvolved in the activation of T regulatory cells and myeloid derived suppressor cells, we hypothesized that it could reduce both antiviral and antitumoral immune surveillances in cervical intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (SCC).
Design: The study population comprised 6 invasive SCC of the uterine cervix, 10 CIN cases, and non-neoplastic contiguous squamous mucosa from 7 cases. Immunohistochemical staining was performed for: signal transducer and activator of transcription (STAT) 3, phosphorylated on tyrosine 705; CD8, cytotoxic T lymphocytes; FoxP3, T regulatory cells. The expression levels of p-STAT3 in the epithelial cells were graded on a 0 to 3 + scale. Numerical counts of the CD8+, FoxP3+ and nuclear p-STAT3 + lymphocytes were carried out in the intratumoral and stromal compartments. Statistical analysis of the data involved ANOVA.
Results: p-STAT3 was overexpressed in the nuclei of the CIN and SCC cells at 1 to 3+ in from 60 to 100% of tumoral nuclei vis-a'-vis the non-neoplastic mucosal epithelium (1+ involving primarily the basal cell layer). This coincided with the statistically significant increase (p<0.05) in the numbers of CD8+, FoxP3+ and p-STAT3 + lymphocytes in the intratumoral epithelium and stroma of the CIN and SCC cases. These are illustrated below:
Conclusions: This study confirms the overexpression and constitutive activation of the STAT3 pathway in CIN and SCC of the uterine cervix with a concomitant increase in the T regulatory (FoxP3+) and p-STAT3 + lymphocytes (the latter to include myeloid derived suppressor cells). This coincides with the scientific literature in supporting a role for the STAT3 pathway in downregulating host immune surveillance in CIN and SCC and identifies the STAT3 pathway as a therapeutic target in this disease.
Category: Gynecologic & Obstetrics
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 169, Monday Morning