(P 112) PREVALENCE AND PROGNOSTIC VALUE OF TARGETABLE RECEPTORS IN EXTRA-UTERINE LEIOMYOSARCOMA

Author(s)

Tanner Mack, MD

Anatomical Pathology Resident
The University of Ottawa / The Ottawa Hospital
Ottawa, Ontario, Canada

Co-Author(s)

BD

Brittany Dingley, MD MPH FRCSC

Surgical Oncology Fellow
The University of Ottawa
Ottawa, Ontario, Canada
Boaz Wong, MD/PhD(c)

Medical Student
The University of Ottawa
Ottawa, Ontario, Canada
Bibianna Purgina, MD

Anatomical Pathologist
The University of Ottawa
Ottawa, Ontario, Canada
Carolyn Nessim, MD, MSc, FRCSC, FACS (she/her/hers)

Surgical Oncologist
University of Ottawa
Ottawa, Ontario, Canada

Objective: Extra-uterine leiomyosarcoma (LMS) shares similar histology but different behavior and immunohistochemical properties with its uterine counterpart. Current available treatments are limited to complete surgical resection with the possible addition of radiation and chemotherapy. There is limited information in the literature to either confirm or refute the presence and significance of targetable receptors in extra-uterine LMS, and what the prognostic value of these receptors may be. The primary objective was to determine the prevalence of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and c-KIT (CD117) in pathologically diagnosed extra-uterine LMS as well as the demographic characteristics of these patients. A secondary objective was to determine the Overall Survival (OS) of patients with extra-uterine LMS and if a correlation between receptor status and prognosis exists.

Methods: A single-center, non-interventional, retrospective, observational cohort study was performed at The Ottawa Hospital between June 2000 and May 2019. Cases were selected from the electronic information system at our facility which services a population of approximately 1.3 million people. Data collected included patient age and sex, tumour size, location, FNCLCC-grade and stage at diagnosis, treatments, and survival outcomes. An immunohistochemistry panel targeting ER, PR, AR, and CD117 was performed on the best representative formalin-fixed paraffin embedded tissue block. Positive staining was recorded in decile intervals and scored by two pathologists. Descriptive statistics were then performed to summarize continuous and categorical variables. Kaplan-Meier survival curves were plotted and analyzed for significance using the Mantel-Cox log-rank test. All data was analyzed using GraphPad Prism 9 and RedCAP software’s.

Results: A total of 44 patients with a diagnosis of extra-uterine LMS were identified, 13 of which were excluded due to lack of clinical information or insufficient biomarker data resulting in a total of 31 cases analyzed. Our cohort consisted of 14 (45.2%) males and 17 (54.8%) females with a median age of 75 years (range 29 to 94 years). All tumours were primary in location to the following anatomical sites: 10 (32.3%) retroperitoneal, 9 (29.0%) extremities, 5 (16.1%) visceral/abdominal/pelvic, 3 (9.7%) cutaneous, 3 (9.7%) thoracic, and 1 (3.2%) head and neck. Tumors had a median size of 58 mm (range 1.4 to 230 mm), with FNLCC-grades as follows: 12 (38.7%) grade 1, 10 (32.3%) grade 2, and 9 (29.0%) grade 3. Systemic therapy was given in 3 (9.68%) patients and radiation therapy in 14 (45.16%) patients. Negative surgical resection margins were achieved in 30 (96.8%) patients. Immunohistochemistry was performed on 17 (54.8%) excision specimens and 14 (45.2%) biopsy specimens with positive staining reported as follows: 1 (3.2%) ER, 5 (16.1%) PR, 11 (35.5%) AR, and 15 (48.4%) CD117. Most tumours that stained positive had focal and weak staining with 78.8% of all positive staining being within the 1-10% decile. Finally, the estimated 5-year OS for all cases was 83.9% with 9 events occurring over the observed period and a median follow up 54.5 months (range 1.7 to 142.2 months) post-surgery. There were no statistically significant differences in OS with cases that had positive receptors for CD117 (p=0.2648), AR (p=0.3269), or PR (p=0.7863).

Conclusion: In our study we assessed the immunophenotype of extra-uterine LMS using common laboratory antibodies directed against ER, PR, AR and CD117. In most cases, all four receptors did not show frequent or strong staining. In addition, survival analysis did not show any statistically significant differences between receptor expression and OS. Given the limitations in small sample size, these negative findings can only suggest against the potential effectiveness of targeted therapeutics such as Letrozole, Bicalutamide, or Imatinib in treating extra-uterine LMS. Future studies include using next generation sequencing to investigate other potential clinically actionable drug targets.