Protein analysis aids in planning treatment of vulvar cancer

A study published in the journal Human Pathology shows that tumors whose cells heterogeneously express epidermal growth factor receptor are the most dangerous.

By Karina Toledo

Agência FAPESP – A study conducted at the A.C. Camargo Cancer Center and published in the journal Human Pathology reveals that analysis of the expression of a protein known as epidermal growth factor receptor (EGFR) in vulvar tumors may be critical to determining patient prognosis and treatment.

This is because EGFR is related to a tumor’s capacity to multiply and migrate to other locations in the body, researcher Rafael Malignly Rocha explained to Agência FAPESP.

“Our findings, as expected, indicated that the tumors that do not express EGFR are those that best respond to standard treatment and whose carriers have better survival outcomes. What was surprising was to discover that in mixed tumors, in which some of the cells express this receptor and others do not, the prognosis is worse than for tumors in which all of the cells express EGFR,” Rocha explained.

The research study was conducted during the doctoral work of FAPESP scholarship recipient Beatriz de Milo Maya, under the mentorship of Rocha.

The researchers analyzed 150 samples from carriers of vulvar squamous cell carcinoma treated at the A.C. Camargo Cancer Center between 1979 and 2007. Using immunohistochemical analyses, the researchers determined whether the tumor cells expressed EGFR.

By linking the results of the analyses with the patients’ clinical data, the researchers determined that carriers of tumors with expression heterogeneity had worse survival outcomes.

“In these cases, the cells of a single tumor responded differently to the standard treatment. We believe that tumors with different cell subpopulations have greater adaptive capacity and therefore better conditions for promoting metastasis,” Rocha explained.

Routine analysis

According to Rocha, analysis of EGFR expression is already part of the clinical routine for other types of cancer, so the method will be relatively easy to adopt for monitoring vulvar tumors.

The researcher also believes that clinical tests should be performed on existing drugs that are able to inhibit EGFR expression to determine whether these drugs are effective in treating vulvar tumors with homogeneous or heterogeneous expression.

“We need to look at cancer as a highly heterogeneous disease. A single therapeutic alternative therefore may not be enough. We are increasingly seeing that combinations of specific drugs suited to each individual case may help to achieve better results,” he argued.

According to Rocha, the current standard treatment for vulvar cancer includes chemotherapy, radiation therapy and surgical resection of the tumor. The procedures tend to be invasive and have a strong psychosexual impact on patients. “Our goals are to study the molecular biology of the cancer and to find therapeutic alternatives that are less destructive,” he said.

The researcher considers vulvar cancer to be a neglected disease throughout the world, mainly because it is associated with sexual behavior that is thought of as promiscuous. Nearly 40% of all cases are related to previous infections with HPV and affect young women.

The disease accounts for nearly 3% to 5% of female genital tract neoplasias, with a global incidence of 100,000 cases per year. The main symptoms include itching at the site of the lesion, ulceration, bleeding, secretion and the appearance of warts. In certain cases, patients may present urinary dysfunction.

Variable gene expression

In a second analysis, whose findings are expected to be published soon, the group from A.C. Camargo compared gene expression between the 150 tumor samples and healthy vulvar cells.

“We screened more than 20,000 genes to see which were differentially expressed in samples of cancer and in normal tissue. I can safely say that we found two differentially expressed genes in vulvar cancer and that this difference is related to their copy number gain, besides being related to worse patient prognosis,” Rocha explained.

The related article, “EGFR expression in vulvar cancer: clinical implications and tumor heterogeneity” (doi: 10.1016/j.humpath.2014.01.015), can be accessed at www.sciencedirect.com/science/article/pii/S0046817714000513.