Abstract
Osseous metaplasia (OM) is rarely observed in colorectal cancer (incidence < 0.4% in rectal cancer), where it has a non-specific clinical presentation and unknown pathogenesis. Here, we report three cases of colorectal carcinoma with OM and propose a new hypothesis. All three patients (two males and one female) were Chinese and had different sites of colorectal carcinoma with OM: rectum, sigmoid colon, and appendix. The pathologic diagnoses were serrated adenocarcinoma; moderately to poorly differentiated adenocarcinoma with micropapillary carcinoma and cribriform comedo-type adenocarcinoma; and mucinous adenocarcinoma, respectively. Clinical follow-up showed that one patient died 5 months after surgery, but the others are alive after 68 months and 53 months. Immunohistochemistry revealed that CD44, MAPK, MDM2, OPN and PEDF were expressed by both tumor cells and stromal cells, while P53 was expressed only by tumor cells. KRAS/NRAS/BRAF genotyping revealed different KRAS mutations in each of the three cases, but the NRAS and BRAF exons were all wild-type. These findings suggest OM has no relation with NRAS and BRAF mutation, and it is uncertain whether there is a relationship between ossification and KRAS mutation. OPN, MAPK, MDM2, P53, PEDF and CD44 may act as osteogenic factors in colorectal cancer with OM.