Editorial: an obsession with subtyping gastric cancer

Abstract

My English revisers always correct my ambiguous usage of ‘‘type’’ and ‘‘subtype’’ to describe cancers. I sometimes use ‘‘cancer type’’ in the context of adenocarcinoma versus squamous cell carcinoma, but at other times I use it in the context of gastric cancer versus lung cancer. I am not sure whether to refer to ‘‘adenocarcinoma of the lung’’ as a type or a subtype when discussing a grandiose topic such as the ‘‘histopathology of human cancer.’’ Categorization was part of human nature even before the work of Carl von Linne, but no categorizations can be more complicated than pathological categorizations, especially those based on the microscopic morphology of cancer cells. Why do we categorize tumors? Lung cancer and gastric cancer are different, so their therapy, care, and prevention measures should also differ. Why must we differentiate between adenocarcinoma and squamous cell carcinoma among cancers arising within the same organ (such as the lung)? Again, therapy (probably), care (possibly), and prevention measures (definitely: for example, avoiding smoking to prevent squamous cell carcinoma of the lung) should be modified according to the tumor category. Then, should we also discriminate among the subtypes of adenocarcinoma of the gastrointestinal tract, such as welldifferentiated versus poorly differentiated? Yes, we know of biological differences between these two subtypes, and a principle of general pathology teaches us that the latter is generally associated with a poorer prognosis. However, we are not sure whether this difference is notable when comparing subtypes at different stages (for example, earlystage poorly differentiated cancer versus advanced-stage well-differentiated cancer). Heterogeneity within a single tumor and heterogeneity among many similar-looking tumors had been known before the era of massive parallel sequencing revolutionized molecular concepts regarding human cancer. One of my good friends, a confident pulmonary surgeon, once said to me, ‘‘No histological description is needed in a breast cancer pathology report; just 3 or 4 immunohistological scores including HER2, hormone receptors, and maybe a proliferation indicator, such as the Ki-67 labeling index.’’ In the era of companion diagnostics, categorization based on morphology, which is often subjective, may only further complicate clinical cancer management and create an unnecessary burden on pathologists. Actually, every few years the name, subtype categories, and requirements for describing questionable attributes change for unknown reasons and without any emerging evidence but simply because they have been labeled as being a ‘‘general rule.’’ On the other hand, as we approach the brink of personal medicine, the ultimate tumor subtyping—in which the whole genome sequencing of tumor DNA up to the singlecell level will be performed—is appearing on the horizon. The cost of such analyses is becoming less and less and is much less than that of hiring technicians who can make beautifully stained sections. In contrast to morphological classifications, the DNA sequence data can directly pinpoint target molecules that clinicians can then use as a starting point for individualized therapy. Complaints of late This editorial refers to the article doi:10.1007/s10120-012-0226-6.