Salivary gland cancers (SGCs) are diagnosed using histopathological examination, which significantly contributes to their progression, including lymph node/distant metastasis or local recurrence. In the current World Health Organization (WHO) Classification of Head and Neck Tumors: Salivary Glands (5th edition), malignant and benign epithelial tumors are classified into 21 and 15 tumor types, respectively. All malignant tumors have the potential for lymph node/distant metastasis or local recurrence. In particular, mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), salivary duct carcinoma, salivary carcinoma, not otherwise specified (NOS, formerly known as adenocarcinoma, NOS), myoepithelial carcinoma, epithelial–myoepithelial carcinoma, and carcinoma ex pleomorphic adenoma (PA) are relatively prevalent. High-grade transformation is an important aspect of tumor progression in SGCs. MEC, AdCC, salivary carcinoma, and NOS have a distinct grading system; however, a universal histological grading system for SGCs has not yet been recommended. Conversely, PA is considered benign; nonetheless, it should be cautiously treated to avoid the development of metastasizing/recurrent PA. The aim of this review is to describe the current histopathological aspects of the prognostic factors for SGCs and discuss the genes or molecules used as diagnostic tools that might have treatment target potential in the future.

Endometrioid carcinoma (EC) and clear cell carcinoma (CC) are associated with endometrial tissue hyperplasia and endometriosis, and they occur in the endometrium and ovaries. However, detailed differences between these tumors based on immunostaining are unclear; therefore, in this study, we aimed to analyze the clinicopathological correlations between these tumors using immunostaining and to develop new treatments based on histological subtypes. Immunohistochemistry was used to investigate differentially expressed hypoxia-associated molecules (hypoxia-inducible factor-1 subunit alpha [HIF-1α], forkhead box O1, prostate-specific membrane antigen, signal transducer and activator of transcription 3 [STAT3], hepatocyte nuclear factor 1β [HNF-1β], aquaporin-3, and vimentin [VIM]) between these carcinomas because of the reported association between CC and ischemia. Immunostaining and clinicopathological data from 70 patients (21 uterine endometrioid carcinomas [UECs], 9 uterine cell carcinomas, 20 ovarian endometrioid carcinomas [OECs], and 20 ovarian cell carcinomas [OCCs]) were compared. HIF-1α and prostate-specific membrane antigen expression levels were higher in UEC and OCC than in uterine cell carcinomas and OEC. STAT3 was slightly overexpressed in UEC. Additionally, forkhead box O1 expression was either absent or significantly attenuated in all ECs. VIM and AQ3 were highly expressed in UEC, whereas HNF-1β expression was higher in OCC. UEC, OEC, and OCC were more common in the uterine fundus, left ovary, and right ovary, respectively. Ovarian endometriosis was strongly associated with EC. Our findings suggest that UEC and OCC share a carcinogenic pathway that involves HIF-1α induction under hypoxic conditions via STAT3 expression, resulting in angiogenesis. Furthermore, the anatomical position of carcinomas may contribute to their carcinogenesis. Finally, aquaporin-3 and VIM demonstrate strong potential as biomarkers for UEC, whereas HNF-1β expression is a crucial factor in CC development. These differences in tumor site and histological subtypes shown in this study will lead to the establishment of treatment based on histological and immunohistological classification.