Chiu-Hsuan Cheng

Topological Distribution of the Sex Hormone Receptor Expressions Highlights the Importance of Stromal ERα and Epithelial PR in Malignant Transformation of the Uterine Cervix

To investigate the changes of ERα and PRs in the epithelium and stroma of normal and neoplastic uterine cervix. Two pathologists independently scored the expression levels of ERα, PR(A+B), and PRB in the stroma and epithelium of normal, cervical intraepithelial neoplasia grade 2 and 3 (CIN2/3), carcinoma in situ (CIS), and invasive cervical carcinoma (ICC) specimens. Sex hormone receptors were abundantly expressed in the stroma compared to the epithelium or carcinoma of the cervix. Stromal ERα was progressively upregulated during cervical carcinogenesis, with an immunoreactive score (IRS) of 1.3 ± 1.5, 2.1 ± 1.9, and 3.6 ± 3.3 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). By contrast, epithelial PR(A+B) and PRB were downregulated, with IRS of 0.4 ± 0.7 and 0.5 ± 0.8, 0.1 ± 0.4 and 0.2 ± 0.6, and 0.1 ± 0.6 and 0.1 ± 0.4 in the CIN2/3, CIS, and ICC groups, respectively (p < 0.001). During the CIN2/3 transition, the coexpression relationship between ERα and PRs began to break down. Although epithelial PR(A+B) was downregulated, stromal PR(A+B) and PRB were upregulated with IRS of 2.0 ± 2.0 and 2.0 ± 1.9 as well as 2.1 ± 2.3 and 3.2 ± 3.2 in the CIS (p = 0.009) and ICC groups (p < 0.001), respectively. After complete transformation, the stromal PRB was significantly upregulated, and its loss was related to more distant metastasis and poorer prognosis. The results of this study highlight the carcinogenic role of stromal ERα, the tumor suppressor role of epithelial PRs, and the importance of stromal PRB in the development of cervical cancer; they can be used as a basis for developing prevention and treatment strategies for this disease.

Anti-Estrogen Therapy Achieves Complete Remission and Stability in Recurrent Cervical Cancer: A Case Study

BACKGROUND Studies using transgenic mouse models have demonstrated that estrogen is necessary for the development of cervical cancer, particularly in tissues responsive to estrogen. Estrogen also protects cervical cancer cells from apoptosis, suggesting its role in the survival and persistence of cancer cells. CASE REPORT An 84-year-old woman with diabetes mellitus, hypertension, and stage III chronic renal failure was diagnosed with cervical squamous cell carcinoma, FIGO stage IB2. She underwent complete concurrent chemoradiotherapy, but central recurrence was found 9 months later. However, instead of salvage chemotherapy, substitutionary anti-estrogens were given due to her poor medical condition and advanced age. Complete remission was noted after tamoxifen therapy. Since the cervical cancer relapsed again 40 months after tamoxifen use, the anti-estrogen therapy was shifted to letrozole. The SCC-Ag level decreased dramatically after letrozole therapy, and disease stability was achieved until 29 months afterward. After 5 years and 9 months of anti-estrogen use only, the patient died due to noncancer-related pneumonia and heart failure. CONCLUSIONS This report demonstrates the tumor-stabilizing and therapeutic effect of anti-estrogens in the treatment of squamous cervical carcinoma. Further clinical trials are warranted to evaluate the efficacy of anti-estrogen therapy in cervical cancer patients.