Robert Samuelson

Discovery of candidate tumor biomarkers for treatment with intraperitoneal chemotherapy for ovarian cancer.

Tumor mRNA expression was used to discover genes associated with worse survival or no survival benefit after intraperitoneal (IP) chemotherapy. Data for high grade serous ovarian cancer patients treated with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Progression free survival (PFS) and overall survival (OS) were compared between IP and IV groups using Kaplan-Meier analysis and Cox regression. Validations were performed by analyses of microarray and RNA-Seq mRNA expression data. PFS and OS were compared between IP and IV groups by permutation testing stratified by gene expression. P-values are two-tailed. IP chemotherapy increased PFS (26.7 vs 16.0 months, HR 0.43 (0.28–0.66), p = 0.0001) and OS (49.6 vs 38.2 months, HR 0.46 (0.25–0.83), p = 0.01). Increased expression of NCAM2 and TSHR and decreased expression of GCNT1 was associated with decreased PFS and OS after IV chemotherapy (p < 0.05). High tumor expression of LMAN2, FZD4, FZD5, or STT3A was associated with no significant PFS increase after IP compared to IV chemotherapy. Low expression of APC2 and high expression of FUT9 was associated with 5.5 and 7.2 months, respectively, decreased OS after IP compared to IV chemotherapy (p ≤ 0.007).

Clinical utility of chromogranin A and octreotide in large cell neuro endocrine carcinoma of the uterine corpus.

Primary neuroendocrine tumors of the female genital tract have been described in the cervix, ovaries and uterus. Large cell neuroendocrine carcinoma (LCNC) of the uterine corpus is the least common and appears to behave the most aggressively. We report a rare case of a large cell neuroendocrine tumor of the endometrium. These tumors are not well characterized, unlike neuroendocrine tumors of the uterine cervix. Consequently, the optimal management remains still unclear. The treatment of our case consisted of surgery, radiotherapy, chemotherapy, and octreotide. Despite the aggressive treatment, the patient died of disease progression 12 months after the initial diagnosis. We discuss the diagnosis, prognosis, and treatment options for LCNC of the genital tract, and potential future therapeutics.

Mullerian adenosarcoma of the cervix: Report of two large tumors with sarcomatous overgrowth or heterologous elements

Highlights • Two cases of large cervical mullerian adenosarcoma with sarcomatous overgrowth or heterologous elements and contrasting survival outcomes are reported.• When the diagnosis of mullerian adenosarcoma is uncertain or suspected, review of pathology by a national expert may be considered.• Rhabdomyoblastic differentiation of mullerian adenosarcoma may be a more aggressive histologic type.

Recent Advancements in Prognostic Factors of Epithelial Ovarian Carcinoma

Ovarian cancer remains the most common cause of gynecologic cancer-related death among women in developed countries. Nevertheless, subgroups of ovarian cancer patients experience relatively longer survival. Efforts to identify prognostic factors that characterize such patients are ongoing, with investigational areas including tumor characteristics, surgical management, inheritance patterns, immunologic factors, and genomic patterns. This review discusses various demographic, clinical, and molecular factors implicating longevity and ovarian cancer survival. Continued efforts at identifying these prognosticators may result in invaluable adjuncts to the treatment of ovarian cancer, with the ultimate goal of advancing patient care.

Human papillomavirus- associated cancers as acquired immunodeficiency syndrome defining illnesses

Abstract The Centers for Disease Control currently report cervical, vulvar, vaginal, anal and some head and neck cancers as human papillomavirus (HPV)-associated cancers. Only cervical cancer is listed amongst acquired immunodeficiency syndrome (AIDS) defining illnesses. All of these cancers may represent progression of the immunocompromised state with the inability to eradicate viral infection. This study reports the case of a 27-year old HIV positive female presenting with a persistent right vulvar exophytic lesion. High-risk HPV analysis and immunostaining for P16 were both positive. A biopsy of the lesion revealed invasive squamous cell carcinoma. The patient underwent neoadjuvant radiation and chemotherapy followed by a radical vulvectomy. During treatment, her CD4 T-lymphocyte count decreased to 120 advancing her condition from HIV to AIDS. This case suggests that all HPV-associated cancers should be included as AIDS defining illnesses.

Urine Protein/Creatinine Ratios during Labor: A Prospective Observational Study.

Purpose To evaluate the utility of urine protein/creatinine ratio (uPCR) measurements among healthy parturients at term we performed a prospective cohort study at a community teaching hospital. Methods Serial urine samples were collected. Ninety-three women contributed 284 urine samples. uPCRs were determined. Multiple imputation and paired sampled analysis was performed when appropriate. Results Two-thirds (63/93) of women had at least one measured uPCR ≥ 0.3. One-third (31/93) had a uPCR ≥ 0.3 at admission, including 39.1% (9/23) of women not in labor. Median (IQR) uPCRs increased during labor and after delivery: latent phase/no labor, 0.15 (0.06–0.32); active phase, 0.29 (0.10–0.58); early postpartum, 0.45 (0.18–1.36) (all p < 0.04). Median uPCRs were significantly < 0.3 in the latent phase and significantly > 0.3 in the immediate postpartum period (p < 0.01). Women who labored before cesarean delivery had the highest early postpartum uPCRs: median (IQR) 1.16 (0.39–1.80). A negative urine dipstick protein result did not exclude uPCR ≥ 0.3. uPCRs were similar when compared by method of urine collection. Conclusion uPCR ≥ 0.3 is common among healthy women with uncomplicated pregnancies at term. uPCR increases during labor and is not a reliable measure of pathologic proteinuria at term or during the peripartum period.

Metastatic Uterine Leiomyosarcoma Involving Bilateral Ovarian Stroma without Capsular Involvement Implies a Local Route of Hematogenous Dissemination

Uterine sarcomas spread via lymphatic and hematogenous dissemination, direct extension, or transtubal transport. Distant metastasis often involves the lungs. Ovarian metastasis is uncommon. Here we present an unusual case of a large, high-grade uLMS with metastatic disease internal to both ovaries without capsular involvement or other abdominal diseases, and discovered in a patient with distant metastases to the lungs, suggesting likely hematogenous dissemination of uLMS to the ovaries in this case. Knowledge of usual uLMS metastases may influence surgical management in select cases.

Abstract 4754: Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer

Objective. To test if hormone or growth factor receptor expression is associated with survival among patients with high grade serous ovarian cancer (HGS OvCa) we analyzed tumor mRNA expression microarray and clinical data from The Cancer Genome Atlas (TCGA). Methods. HGS OvCa patients were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy. Multivariate Cox proportional-hazards regression tested associations of expression of 9 hormone or growth factor receptors with progression free survival (PFS) and overall survival (OS). Hazard ratios are hazard per each one standard deviation increase in gene expression. Expression was analyzed as a continuous variable by restricted mean survival analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Expression of ESR1, PGR, FSHR, LHCGR, MET, and EGFR were not associated with PFS or OS. TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and PFS (HR 1.18 (1.05-1.33), p = 0.006) among IV-only treated patients. ERBB2 expression was associated with decreased OS (HR 1.48 (1.05-2.10), p = 0.027) among patients who received IP chemotherapy. Using multigene (ESR2, PGR, TSHR, and ERBB2) analysis, among the IP group, ERBB2 (HR 1.76 (1.11-2.79), p = 0.015) and ESR2 (HR 0.28 (0.08-0.93), p = 0.037) were associated with OS. Only TSHR expression was associated with decreased OS (HR 1.22 (1.06-1.41), p = 0.005) and decreased PFS (HR 1.18 (1.05-1.33), p = 0.007) on multigene analysis of IV-only treated patients. OS and PFS decreased steeply at high expression of TSHR and ERBB2. Among patients with upper 10th percentile TSHR expression, no significant difference in mean OS or PFS was observed between patients treated with IP versus IV-only chemotherapy. Patients with lower TSHR expression ( Conclusions. Among HGS OvCa patients treated with IV-only chemotherapy, increased tumor TSHR expression was associated with decreased OS and PFS. High TSHR expression characterized patients who did not benefit from IP chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Overexpression of TSH and ERBB2 (HER2) receptors is associated with sharply decreased survival in high grade serous ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4754.

Abstract 4753: Ovarian cancer stem cell marker ALDH1A2 is a candidate biomarker for patient selection for intraperitoneal chemotherapy

Objective. To evaluate ovarian cancer stem cells as predictors of survival we analyzed associations of cancer stem cell markers ALDH1, CD117 and CD133 with survival outcomes among patients with high grade serous ovarian cancer (HGS OvCa). Methods. Data from HGS OvCa patients who were surgically staged prior to treatment with IP (n = 90) or IV-only (n = 398) chemotherapy was obtained from The Cancer Genome Atlas. Multivariate Cox proportional-hazards regression tested associations of tumor mRNA expression of 5 cancer stem cell markers with progression free survival (PFS) and overall survival (OS). Expression was analyzed as a continuous variable by restricted mean survival (RMS) analysis. Mean PFS or OS were compared between IP and IV groups by permutation testing stratified by expression. P-values were two-tailed. Results. Increased tumor ALDH1A2 expression was associated with decreased OS among patients treated with IP chemotherapy, HR 2.36 (1.16-4.80), p = 0.017. IP treated patients with upper 20th percentile ALDH1A2 expression had decreased OS compared to bottom 20th percentile expression (30.4 versus 51.1 months, -20.7 months difference, p = 0.017). RMS curves for PFS and OS of IP versus IV treated patients crossed at high ALDH1A2 expression, indicating that IP treated patients had decreased survival compared to IV-only treated patients. Patients with upper 20th percentile ALDH1A2 expression treated with IP versus IV-only chemotherapy had no difference in mean PFS (21.3 versus 21.6 months, -0.3 months difference, p = 0.67) and decreased OS (30.4 versus 35.3 months, -4.9 months difference, p Conclusions. High primary tumor ALDH1A2 expression was independently associated with significantly decreased OS among patients treated with IP chemotherapy. High ALDH1A2 was associated with lack of benefit or decreased survival among patients treated with IP compared to IV-only adjuvant chemotherapy. Citation Format: Brandon-Luke L. Seagle, Monica Dandapani, Chen Hui Luo, Claire Hoppenot, Robert Samuelson, Kevin H. Eng, Kunle Odunsi, Shohreh Shahabi. Ovarian cancer stem cell marker ALDH1A2 is a candidate biomarker for patient selection for intraperitoneal chemotherapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4753.

Feasibility, sensitivity, and specificity of postprocedure peritoneal cytology

The objective of this study was to determine the feasibility and diagnostic performance of cytopathologic evaluation of postprocedure washings collected after hysterectomy for gynecologic cancer. A total of 92 cases of hysterectomy for malignancy having cytology reports of both pre- and postprocedure washings were retrospectively identified. In all, 98.7% of preprocedure and 99.3% of postprocedure washings (P = 1.00) were satisfactory for cytopathology. Discordance regarding the observation of malignant cells between preprocedure and postprocedure washings was insignificant (P = .267). The sensitivity of postprocedure cytology for detecting malignant cells in cases of positive peritoneal histology was significantly lower than the sensitivity of preprocedure cytology (28.6% vs 57.1%, P = .041), with similar specificities (both 94%). Four patients with endometrial cancer having negative preprocedure peritoneal cytology were discovered to have positive postprocedure cytology. Postprocedure peritoneal cytology is feasible and may benefit patients with early-stage cancer by increasing the detection of microscopic peritoneal metastasis or cancer cell seeding during surgery.