MCI researchers study rare gynecologic melanomas

Gynecologic oncology fellow Annelise Wilhite, M.D., works in the lab at the Mitchell Cancer Institute.

Using molecular profiling, physician scientists at the USA Health Mitchell Cancer Institute investigated molecular differences between vulvar and vaginal melanomas, two rare forms of cancer that often are studied as a single entity – vulvovaginal melanoma. 

They concluded that despite the differences in patient survival, which served as the impetus for the research, the two melanomas share similar molecular and immune characteristics, and should continue to be studied together.

Annelise Wilhite, M.D., gives a presentation at the Society
of Gynecologic Oncology's Annual Meeting on Women's
Cancer in Phoenix, Arizona.

Annelise Wilhite, M.D, a gynecologic oncology fellow at the Mitchell Cancer Institute, gave an oral presentation on this research during a master class at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer in Phoenix, Arizona, in March.

“We found that these tumors have similar molecular and immune profiles, which could be one reason they both respond poorly to this type of targeted therapy compared with the cutaneous melanoma patients,” Wilhite said. “Especially in light of the rarity of the disease, it makes sense to continue to study them as a single entity.”

Wilhite led the project under the mentorship of Nathaniel Jones, M.D., a gynecologic oncologist and assistant professor of interdisciplinary clinical oncology. Together, they worked with Caris Life Sciences to obtain molecular profiling on 183 vulvar and vaginal melanomas. They discovered that the samples shared similar molecular profiles, with relatively high rates of alternations in the KIT gene and low rates of BRAF gene mutations. “The two had a complete lack of TMB-H tumors and similar PD-L1 (protein) expression, and these are markers of response for immune-targeted therapy,” Wilhite said. “Their immune microenvironment was similar, predominated by myeloid dendritic cells and low rates of cytotoxic and helper T cells.” 

They found that vulvar melanoma patients have a better overall survival than vaginal melanoma patients, which is consistent with previous studies. However, the survival advantage disappeared when the researchers compared only those patients who received immune-targeted therapy. 

This type of immune-targeted therapy targets T cells to help them fight the tumor using the patient’s own immune system, and they often are successful in treating many types of melanomas, Wilhite said, adding that the lack of immune markers and lack of T cells could be responsible for the poor response to treatment among the vulvovaginal melanoma patients.  

“Our next steps will be trying to identify other ways to target vulvovaginal melanomas and their immune microenvironments,” she said. “There are ongoing studies looking at new agents that target other aspects of the immune system, and it will be interesting to see if these agents improve outcomes for vulvovaginal melanoma patients.”   

Other researchers and institutions involved in the project included the Caris Precision Oncology Alliance. The collaboration included gynecologic oncologists and melanoma specialists from institutions around the United States.