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Background: The influence of sex hormone and insulin/insulin-like growth factor (IGF) axis signaling on endometrial cancer recurrence is unknown. We evaluated these pathways in a prospective cohort of Gynecologic Oncology Group (GOG)0210 trial endometrial adenocarcinoma patients., Methods: Stage II-IV patients ( N = 816) were included in this study. Pretreatment specimens were tested for tumor mRNA and protein expression of IGF1, IGF2 , IGF-binding proteins ( IGFBP ) -1 and -3 , insulin (IR) and IGF-I receptors (IGF1R), phosphorylated IR/IGF1R (pIGF1R/pIR), and estrogen (ER) and progesterone receptors (PR) using qPCR and IHC. Serum concentrations of insulin, IGF-I, IGFBP-3, estradiol, estrone, and sex hormone binding globulin were measured. HRs and 95% confidence intervals (CI) for progression-free survival were calculated from Cox models adjusting for age, stage, and grade., Results: Recurrence occurred in 280 (34%) cases during a median of 4.6 years of follow-up. ER positivity (HR, 0.67; 95% CI, 0.47-0.95), IR positivity (HR, 0.53; 95% CI, 0.29-0.98), and circulating IGF-I (highest vs. lowest quartile: HR, 0.66; 95% CI, 0.47-0.92) were inversely associated with recurrence risk. Circulating estradiol (highest vs. lowest tertile: HR, 1.55; 95% CI, 1.02-2.36) and pIGF1R/pIR positivity (HR, 1.40; 95% CI, 1.02-1.92) were associated with increased recurrence risk., Conclusions: Circulating estradiol and tumor tissue phosphorylated (activated) IGR1R/IR were independently associated with higher risk of recurrence in patients with endometrial cancer., Impact: This study may inform future clinical trials of endocrine-targeted adjuvant therapies in patients with endometrial cancer that could include baseline assessment of serum and tissue biomarkers of estradiol and insulin signaling pathways., (©2021 American Association for Cancer Research.)

Objective: To evaluate surgical, clinical, and pathologic outcomes of patients with endometrial cancer managed with primary surgery when stratified by body mass index (BMI)., Methods: A review of 356 consecutive patients undergoing primary surgical management of endometrial carcinoma by a single gynecologic oncology service from 1997 to 2003 was undertaken. Patients were divided into three groups based on preoperative BMI. Data regarding surgical and pathologic outcomes were compared., Results: Twenty-two percent of patients had a BMI >40, 38% were 30-40, and 40% were <30. Overall, 90% underwent some surgical staging, including 93%, 92%, and 81% of those with a BMI <30, 30-40, and >40, respectively. In fully staged patients, a median 23 lymph nodes were removed in all groups, without a significant difference in the number of aortic nodes recovered between the heaviest and lightest groups. Aortic lymphadenectomy was performed in 48% patients with BMI >40 compared with 74% of patients with BMI <30. Intraoperative and postoperative complications were rare and similar between groups. Patients with BMI >40 were more commonly diagnosed with grade 1 tumor than patients with BMI <30. Rates of nodal metastasis were similar between groups and occurred in 11% of patients overall. In those with a BMI >40, extrauterine disease was encountered in 12% of patients., Conclusions: While surgical staging of morbidly obese patients is difficult, adequate lymphadenectomy can be performed safely; although aortic nodes are less commonly resected in this population. Staging remains important in obese women, as the risk of extrauterine disease, including lymph node metastasis, is similar to that in women with ideal body weight.

In a woman with cervical cancer and a distant lesion, the histologic distinction of metastatic cervical cancer versus another primary tumor or metastases from another cancer can be difficult and has important clinical implications. Criteria for inclusion in the study were a history of primary cervical cancer and a new lesion in which the pathologic differential diagnosis was metastatic cervical cancer versus new primary versus metastatic ovarian carcinoma. Ten cases were identified. The cervical cancers and the other lesion(s) were tested for human papillomavirus DNA by in situ hybridization and human papillomavirus RNA (E6/E7) by reverse transcriptase in situ polymerase chain reaction. Human papillomavirus DNA was detected in the primary cervical cancer by in situ hybridization in five of nine cases; viral RNA was detected by reverse transcriptase in situ polymerase chain reaction in nine of nine cases (one case was not available for viral testing). In six cases, human papillomavirus was detected in the subsequent lesion (three lung, one cervical lymph node, two retroperitoneum), documenting the latter was metastatic cervical cancer. Human papillomavirus was not detected in the other four cases (two lung, two retroperitoneum in women with ovarian cancer), documenting that they were either primary lung cancers or metastatic ovarian cancers, respectively. Reverse transcriptase in situ polymerase chain reaction for human papillomavirus RNA is a reliable method to differentiate metastatic cervical carcinoma from either a new primary tumor or a metastasis from another cancer.

We report an unusual histopathologic finding in the endometrium from six premenopausal or perimenopausal patients who underwent biopsy for abnormal uterine bleeding. In each case the endometrial stromal cells focally exhibited a pronounced epithelioid appearance; some showed a cord-like trabecular pattern and others a signet-ring-like cell change. All raised the possibility of a metastatic malignancy, particularly from the breast. The epithelioid appearance of the stromal cells appears to be an unusual artifact occurring in a background of secretory change and predecidualization with nonmenstrual breakdown.