Amid Molecular Diagnostic Advances, IHC Retains Significance in Melanoma

Shane A. Meehan, MD

Molecular assays are a driving force in diagnosing a broad array of tumor types, and while molecular diagnostics assays are propelling the field of oncology forward, Shane A. Meehan, MD, emphasizes the important role that immunohistochemistry (IHC) still has—especially for diagnosing melanoma.

“Molecular diagnostics is a new front. It has been around for 5 years,” said Meehan during the 2017 OncLive^® State of the Science Summit^TM on Melanoma and Immuno-Oncology. “IHC has been around for decades. There is almost a tendency to say, ‘Hey, we got these newer molecular diagnostic tests. This is where we need to go.’ In fact, there is still a lot that IHC can help us with.”

OncLive: Could you discuss the highlights of your lecture?

Shane A. Meehan, MD, associate professor, Ronald O. Perelman Department of Dermatology, associate professor, Department of Pathology, director of the Dermatopathology Fellowship Training Program, and director of the Dermatopathology Section at New York University Langone Medical Center in New York, discussed the continued importance of IHC testing, even with the emergence of novel molecular assays, in an interview during the meeting.Meehan: I want oncologists to know about how important IHC is in the analysis of melanocytic lesions. It is important, but there are a limited number of applications and, primarily, the most important application is the use of IHC to determine melanocytic differentiation when one sees a poorly differentiated tumor.

We have, in our armamentarium, a variety of antibodies to use in order to determine that melanocytic differentiation. Those are S100, SOX10, MelanA, HMB45, and there are others. The most sensitive and specific markers are S100 and SOX10 in addition to MelanA. Then, depending on the particular profile of these markers and what particular antigens they can stain, 1 might be more useful for the diagnosis of desmoplastic melanoma than the diagnosis of melanoma in situ.

You can detect these markers with the use of IHC?

Are there any ongoing research studies looking more in depth at these markers?

As dermatopathologists, we weigh the pros and cons of each of these antibodies in how to work up a melanocytic lesion depending on our suspicion of its particular type. There are other markers that we can use besides the melanocytic ones, a lymphatic one called D240, and also a proliferation marker called Ki-67. We have to be wary of the potential pitfalls of any 1 of these markers. We use them all in our assessment in melanocytic lesions as we arrive at the diagnosis of melanoma. Most of these markers that I talked about are only useful in determining the nature of a tumor as being melanocytic. Ki-67 is a proliferation marker. Once we determine that a marker is of a melanocytic lineage—that it’s either melanoma or nevus—we can use other markers, such as Ki-67, a proliferation marker. That would show it’s more likely something atypical, like a melanoma rather than a nevus. A proliferation marker, in that instance, may not show much staining, but if it does show a lot of staining, then we have to be concerned about a melanoma diagnosis. Every few months, another marker comes on the market as the “new kid on the block,” whether or not [it’s really] more sensitive or specific. Over time, we know whether or not a particular marker is tried and true.

An example of a more recent marker is p16, a cyclin kinase inhibitor. Initially, it showed much promise and tends to have decreased expression in melanomas. With experience, it turned out there are issues with regards to specificity with p16, so it is maybe not the “magic bullet” that people thought it would be.

What challenges still exist with pathology in melanoma?

How often are we using tools aside from IHC?

It’s a trend: We do have antibodies that come to light every 6 months or 1 year. However, their true strength lies in their use over time. It can sometimes be 5 years before the sensitivity or the specificity of these particular antibodies is known. One of the important things that IHC can maybe help us with is to act as surrogates for the more in-depth molecular diagnostic studies that are being performed. For example, it’s important to know whether or not a BRAF mutation exists in a particular melanoma because that might inform therapy and [patients might] end up on a BRAF inhibitor, which would be great. It would be nice if there were an IHC test that could act as a surrogate for that BRAF test. A molecular diagnostics test requires more resources and is more expensive. One of the challenges is to come up with markers—IHC and antibodies—that will act as surrogates so that one doesn’t have to perform the molecular diagnostic test. That is something on the forefront.Right now, we are moving towards more molecular diagnostics. However, the nice thing about IHC is that it’s cheaper, quicker, and still has a lot of power in terms of sensitivity and specificity. Molecular diagnostics sounds “sexier,” but there is more detail [in IHC]. You are drilling down on these teeny, tiny antigens in a particular cell type, but it still takes more resources.

What are the key takeaways from your lecture?

The turnaround time in a molecular diagnostic test is much longer than for an IHC test. It will be a while before molecular diagnostics is used exclusively. In terms of differentiating these poorly differentiated tumors and confirming the diagnosis of melanoma in a quick and accurate manner, [IHC] requires a lot fewer resources than molecular diagnostics. That being said, there is a fairly limited application to these particular stains and, if you are interfacing with a dermatopathologist or other pathologists who are using a lot of these stains, it can be confusing and misleading. A limited number of stains can give many simple answers. There doesn’t need to be a large battery [of tests].