PMS2 and neoplasm: Among Lynch syndrome cases, MSH6 mutations are most common and carry intermediate prognosis with later-onset disease, while MSH2 mutations demonstrate more aggressive behavior with earlier presentation, non-endometrioid carcinoma, and higher extrauterine spread. PMS2 mutations (~5%) show the mildest phenotype with best outcomes. However, whether these differences reflect true biological distinctions or confounding by age, surveillance bias, and tumor grade remains controversial, as Lynch-associated cases often benefit from earlier detection through screening programs.