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Gynecologic melanomas: A clinicopathologic and molecular analysis.

Abstract：

OBJECTIVE:Melanoma originating from gynecologic sites (MOGS), including the vulva, vagina, and cervix, is a rare and aggressive form of melanoma with poor long-term clinical outcome. The clinicopathologic features of vulvar and non-vulvar tumors remain relatively understudied, and in contrast to cutaneous melanomas at non-sun-exposed sites, MOGS typically do not harbor BRAF mutations. Thus, we sought to analyze the clinicopathologic and molecular features of MOGS. METHODS:A large retrospective cohort of patients with MOGS (n=59) at a single large academic institution over a 28-year period was identified. Associations among clinicopathologic characteristics were assessed via standard statistical approaches, and clinical outcome was examined using Cox regression analysis. Sanger sequencing was utilized to identify mutations in hotspot regions of BRAF, KIT, NRAS, and CTNNB1. RESULTS:Tumors involving the vagina and/or cervix (non-vulvar) are significantly associated with high-risk clinicopathologic features, including increased tumor thickness, ulceration, positive resection margins, lymph node metastasis, and poor long-term clinical outcome (with increased risk of death due to disease). The aggressive clinical behavior of non-vulvar tumors is independent of advanced clinical stage and lymph node metastasis in multivariate analysis. Targeted molecular analysis confirms an overall low rate of oncogenic mutations in our MOGS cohort, although KIT mutations (particularly in exon 11) are relatively enriched. CONCLUSIONS:Overall, our results show that non-vulvar MOGS are aggressive tumors with poor long-term clinical outcome and indicate that few targeted therapeutic options are currently available to patients with MOGS.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Udager AM,Frisch NK,Hong LJ,Stasenko M,Johnston CM,Liu JR,Chan MP,Harms PW,Fullen DR,Orsini A,Thomas DG,Lowe L,Patel RM

doi

10.1016/j.ygyno.2017.08.023

subject

Has Abstract

pub_date

2017-11-01 00:00:00

pages

351-357

issue

2

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(17)31262-3

journal_volume

147

pub_type

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