Maurie Markman, MD
Editor-in-Chief of OncologyLive
Senior vice president for Clinical Affairs and National Director for Medical Oncology
Cancer Treatment Centers of America, Eastern Regional Medical Center
The role of immunohistochemical markers in assisting the clinical pathologist in the establishment of a specific histological diagnosis of malignant disease is well established. Further, the information provided may be of considerable prognostic significance and indicate a relatively more or less favorable biology associated with the disease process in the individual patient.
Yet while the presence of particular markers on or within tumor cells has long assisted in the selection of specific therapeutic options (eg, estrogen receptor and HER2
status in breast cancer), more recent experience has rather substantially expanded the patient populations and disease entities where such data are of major clinical relevance. Examples include the presence of a KRAS
mutation in metastatic colon cancer, a BRAF
mutation in metastatic melanoma, and ALK
rearrangement in lung cancer.
In an interesting twist on this rapidly evolving story, the presence of specific molecular biomarkers not only may be useful in selecting effective approaches and avoiding ineffective strategies, but also may assist in determining the correct morphologic diagnosis of the particular cancer being examined.
For instance, the important predictive role of the presence of an activating EGFR
mutation in defining a population of individuals with non-small cell lung cancer likely to have the greatest opportunity to experience benefit following treatment with a tyrosine kinase inhibitor of EGFR is well-established.1
It also has been recognized that certain clinical features characterize the patient populations most likely to harbor an activating EGFR
mutation. These characteristics include female sex, non-smoker, Asian ethic background, and adenocarcinoma morphology.
ï»¿However, it remained a rather controversial question as to whether such activating mutations actually occur in patients with pure squamous cell carcinoma of the lung. Similar uncertainties existed with regard to the issue of whether KRAS
mutations are ever seen in this morphologic type of non-small cell lung cancer.
Study of Driver Oncogenes in Lung Tumors2
Conducted at Memorial-Sloan Kettering Cancer Center
95 resected squamous cell carcinomas (SQCC) verified by immunohistochemistry
9EGFR, KRAS, BRAF, PIK3CA, NRAS, AKT1, ERBB2/HER2, and MAP2K1/MEK1 genes, as well as EGFR/KRAS
16 cases previously identified as EGFR/KRAS-mutant SQCC during clinical genotyping reclassified:
10 (63%) cases as adenocarcinoma SQC
5 (31%) cases as poorly differentiated adenocarcinoma with squamoid morphology
1 (6%) case had no follow-up
To address this issue directly, investigators at the Memorial Sloan-Kettering Cancer Center in New York City very carefully examined 95 cases of squamous cell lung cancer seen in their program, an analysis that included a comprehensive panel of immunohistochemical biomarkers.2
Of considerable interest, no cases in this relatively large patient population were found with an activating EGFR
mutation. In addition, there were no KRAS
mutations observed in this group of tumors.