Apoptosis in human pituitary adenomas: a morphologic and in situ end-labeling study

Apoptosis seems to be an important process in normal tissues and in neoplastic lesions. Although electron microscopic features of apoptosis are characteristic, it is difficult to detect apoptotic cells with accuracy by light microscopy. Labeling of intranucleosomal DNA fragmentation can provide information on the apoptotic status of tumors. We studied apoptosis by the in situ end-labeling technique in 85 pituitary adenomas (63 functioning, 22 nonfunctioning). The functioning tumors included 19 somatotroph, 17 lactotroph, 9 mixed growth hormone/prolactin-producing, 2 thyrotroph, and 16 corticotroph adenomas. A few scattered cells displaying characteristic apoptotic changes were observed by histologic examination and electron microscopy. We estimated the apoptotic labeling index (ALI) of the adenomas by quantitating the percentages of positive nuclei. Overall, functioning adenomas showed a significantly higher ALI (5.64%) than did nonfunctioning tumors (1.84%). The ALI was higher in thyrotroph adenomas (10.26%) and lower in corticotroph (5.94%), somatotroph (5.51%), lactotroph (5.25%), and mixed growth hormone/prolactin-producing adenomas (5.11%). In conclusion, in situ end-labeling showed that apoptosis mostly occurs in functioning pituitary adenomas. These data suggest that assessment of apoptosis can be used to evaluate drug effects and to define which adenoma subtypes are more susceptible to drug therapy.