Q. Oncologist: Have I classified the cancer precisely?
a. Tumor classification has critical implications in treatment regimen. For eg. Endometrial tumor (Stage IA), could be endometrioid type or serous type. While patient with endometrioid tumor is provided radiation therapy, the one with serous is given chemotherapy. Another eg. is of Type I and Type II ovarian cancer. While Type I is platinum insensitive, Type II is platinum sensitive and could be investigated for Olaparib eligibility too.
Q. Tumor classification may give crucial information on cancer prognosis. For eg. Differentiated thyroid cancers could be subdivided into Papillary, Follicular and Hurthle. Prognosis of follicular cancer is not as good as Papillary.
Q. Oncologist: But I get tumors classified using H&E staining and/or IHC. Where is the need for genomic analysis?
A(a). For eg. In cancer treatment guidelines, TP53 gene sequencing is considered as primary technique and P53 IHC as surrogate. This is because, if percentage of positively stained cells in P53 IHC slides are less than 5 percent, it may not accurately differentiate between normal and mutated P53 molecule. Similarly, a staining between 50-60 percent of positive cells may not accurately interpret if the sample is of P53 mutant or P53 normal type. In such conditions, TP53 gene sequencing should be performed to get conclusive answer.
(b). For eg. differentiated thyroid cancer can be diagnosed by cytology of FNAC sample. However due to small sample size, cytology results may be inaccurate. Based on that report, Onco-surgeon may or may not opt for complete or partial thyroidectomy. Under conditions where sample amount is small, genomic analysis proves more sensitive and accurate.
Q. Oncologist: I have a patient who have relapsed after rounds of chemo, can you suggest any targeted therapy?
A(a). A molecular pathologist can go over the patient profile and identify the most likely signaling pathway that may be contributing to cancerous tumor. Identifying the signaling pathway that has conked off, gives clues to the oncogenes that must be most likely mutated. It also indicates a list of drugs that are FDA approved or in trails. Molecular pathologist thus suggests minimal set of genes that should be tested to find answer to oncologists question.
Q. Oncologist: I have 35,000/- NGS based test that does entire cancer genomics. Why bother asking molecular pathologist?
A(a). Relevant question to ask, if this NGS panel analyses DNA from blood (mostly for inherited gene mutations resulting in cancer) or from tumor (also includes sporadic gene mutation resulting in cancer)? If you are trying to identify sporadic gene mutation in absence of any family history, an NGS panel focused on blood may not help you.
A(b). Not all NGS panel cover translocations which often results in cancer. For eg., medullary thyroid cancer may result from RET-PTC gene fusion. Such modifications can be captured by NGS only if probes are specifically designed to capture select translocation breakpoints in recurrently rearranged genes. Molecular pathologist can advise you to select appropriate test from a gamut of techniques for genome analysis.
(c). Broad based large NGS panels are designed to include relevant genes from across various cancer. These genes generally indicate FDA approved targeted therapy. However, large retrospective and few prospective studies are underway to determine mutational landscapes in various cancer. These studies continuously update and throw up newer set of genes that indicate targeted therapy, correct classification or prognosis of cancer. Molecular pathologist will help you with specific and edited version of genes to scan for mutation analysis.