Luminal and Basal Subtypes Across Carcinomas: Molecular Programs Beyond Tissue of Origin

Carcinomas originate from polarized epithelia, displaying luminal and basal orientations with distinct biological properties. Regardless of tissue of origin, many carcinomas show luminal or basal traits that are reflected in molecular profiles and are associated with different clinical behaviors and outcomes. Traditionally, cancers have been classified by histology and anatomical site, but accumulating evidence indicates that luminal/basal subtyping reflects shared biological programs that transcend organ boundaries. Breast cancer was the first model in which these subtypes were defined, revealing clear prognostic and therapeutic implications. Subsequent studies have identified similar subtypes in bladder, lung, prostate, pancreatic, and head and neck carcinomas, where basal phenotypes are consistently associated with aggressive disease and distinct vulnerabilities to treatment. In this review, we synthesize advances from the last decade (2010-2024) on the basal-like subtype across epithelial tumors. We summarize key studies applying luminal/basal subtyping in large cohorts of carcinomas and in single tissue tumor types. By integrating these findings, we aim to clarify the current understanding of luminal and basal subtypes in epithelial tumors and outline their potential to refine cancer classification, improve prognostic accuracy, and guide therapeutic decision-making. This perspective supports a biology-driven framework for cancer classification and treatment, moving beyond traditional histological boundaries.