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. 2024 Mar:182:32-38.
doi: 10.1016/j.ygyno.2024.01.015. Epub 2024 Jan 20.

Mesonephric and mesonephric-like adenocarcinomas of gynecologic origin: A single-center experience with molecular characterization, treatment, and oncologic outcomes

Aaron M Praiss  1 , Charlie White  2 , Alexia Iasonos  2 , Pier Selenica  3 , Oliver Zivanovic  4 , Dennis S Chi  4 , Nadeem R Abu-Rustum  4 , Britta Weigelt  3 , Carol Aghajanian  5 , Jeffrey Girshman  6 , Kay J Park  3 , Rachel N Grisham  7
Affiliations

Mesonephric and mesonephric-like adenocarcinomas of gynecologic origin: A single-center experience with molecular characterization, treatment, and oncologic outcomes

Aaron M Praiss et al. Gynecol Oncol. 2024 Mar.

Abstract

Objectives: Mesonephric (MA) and mesonephric-like (MLA) adenocarcinomas are rare cancers, and data on clinical behavior and response to therapy are limited. We sought to report molecular features, treatment, and outcomes of MA/MLA from a single institution.

Methods: Patients with MA (cervix) or MLA (uterus, ovary, other) treated at Memorial Sloan Kettering Cancer Center (MSK) from 1/2008-12/2021 underwent pathologic re-review. For patients with initial treatment at MSK, progression-free survival (PFS1) was calculated as time from initial surgery to progression or death; second PFS (PFS2) was calculated as time from start of treatment for recurrence to subsequent progression or death. Overall survival (OS) was calculated for all patients. Images were retrospectively reviewed to determine treatment response. Somatic genetic alterations were assessed by clinical tumor-normal sequencing (MSK-Integrated Mutation Profiling of Actionable Cancer Targets [MSK-IMPACT]).

Results: Of 81 patients with confirmed gynecologic MA/MLA, 36 received initial treatment at MSK. Sites of origin included cervix (n = 9, 11%), uterus (n = 42, 52%), ovary (n = 28, 35%), and other (n = 2, 2%). Of the 36 patients who received initial treatment at MSK, 20 (56%) recurred; median PFS1 was 33 months (95% CI: 17-not evaluable), median PFS2 was 8.3 months (95% CI: 6.9-14), and median OS was 87 months (95% CI: 58.2-not evaluable). Twenty-six of the 36 patients underwent MSK-IMPACT testing, and 25 (96%) harbored MAPK pathway alterations.

Conclusion: Most patients diagnosed with early-stage disease ultimately recurred. Somatic MAPK signaling pathway mutations appear to be highly prevalent in MA/MLA, and therapeutics that target this pathway are worthy of further study.

Keywords: KRAS; MAPK; Mesonephric adenocarcinoma; Mesonephric-like adenocarcinoma.

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Conflict of interest statement

Declaration of competing interest B. Weigelt reports research funding by Repare Therapeutics, outside the current work. N. R. Abu-Rustum reports grant funding from GRAIL paid to the institution. A. Iasonos reports consulting fees from Mylan. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). D. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. R.N. Grisham reports honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. The other authors do not have potential conflicts of interest to declare.

Figures

Figure 1:
Figure 1:. Histologic features of mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) of gynecologic origin.
Representative hematoxylin-and-eosin photomicrographs of MA and MLA of gynecologic origin. A) MLA of the endometrium, 2X magnification. B) MLA of the endometrium, 10X magnification. C) Progesterone receptor completely negative in tumor with positive internal control of myometrium. D) Thyroid transcription factor 1 (TTF1) positive in tumor cell nuclei.
Figure 2:
Figure 2:. Kaplan-Meier curve demonstrating progression-free survival for first recurrence (PFS1) for patients with mesonephric and mesonephric-like adenocarcinoma of gynecologic origin who received initial care at Memorial Sloan Kettering Cancer Center (MSK), by initial stage.
PFS1 was calculated as the time from surgery to progression (as determined by treating physician) or death.
Figure 3:
Figure 3:. Kaplan-Meier curves demonstrating A) progression-free survival (PFS1), B) second PFS (PFS2), and C) overall survival (OS) for all patients with mesonephric or mesonephric-like adenocarcinoma of gynecologic origin who received initial care at Memorial Sloan Kettering Cancer Center (MSK).
PFS1 was calculated as the time from surgery to progression (as determined by treating physician) or death. PFS2 was calculated as the time from start of treatment for recurrence to progression (as determined by treating physician) or death. OS was calculated as the time from surgery to death or last follow-up.
Figure 4:
Figure 4:. Oncoprint showing recurrent somatic genetic alterations and gene copy number alterations in mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) of gynecologic origin.
Cases are sorted in columns by site of origin, genes in rows, color coded by the legend. Information on mesonephric type, surgical stage, and tissue type (primary/recurrence) are shown in the phenobar on top. *Case harbors a POLE hotspot mutation. MAPK, mitogen-activated protein kinase; SNV, single-nucleotide variant
See this image and copyright information in PMC

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