Pathobiology of pituitary adenomas and carcinomas.
OBJECTIVE
To examine relationships between pituitary tumors and lesion size, invasiveness, resectability, deoxyribonucleic acid ploidy, cell cycle profile, mitotic activity, and immunoreactivity for MIB-1, proliferating cell nuclear antigen (PCNA), p27Kip1, and p53.


METHODS
One hundred fifty-three adenomas of most pathological subtypes, including 20 medically treated and prolactin and growth hormone-containing tumors, as well as 10 premetastatic tumors and 13 pituitary carcinomas, were studied.


RESULTS
Significant (P < 0.05) differences were noted between functional versus nonfunctional adenomas (percent aneuploidy, percent S phase, p27Kip1 labeling indices [LI], male sex, tumor size, and frequency of visual disturbance); Cushing's versus silent adrenocorticotropin adenomas (percent hypertetraploidy, p53 LI, tumor size, visual disturbance, and resectability); untreated versus medically treated prolactin cell adenomas (MIB-1 LI, p53 LI, and resectability); untreated versus medically treated growth hormone-containing adenomas (percent diploidy, percent S phase, MIB-1 LI, p53 LI, and p27 LI); untreated prolactin cell adenomas versus premetastatic tumors (percent hypertetraploidy, PCNA LI, p53 LI, invasiveness, and resectability); untreated growth hormone-containing adenomas versus premetastatic tumors (percent diploidy, percent S phase, PCNA LI, p53 LI, invasiveness, and resectability); Cushing's adenomas versus premetastatic tumors (percent diploidy, percent hypertetraploidy, percent S phase, MIB-1 LI, p53 LI, tumor size, invasiveness, visual disturbance, and resectability); Nelson's adenomas versus premetastatic tumors (p53 LI, tumor size, invasiveness, and resectability); silent adenomas as a whole versus nonfunctional adenomas (percent nondiploid, percent S phase, invasiveness, and respectability); silent adrenocorticotropin adenomas I and II versus silent adenoma Subtype III (invasiveness); silent adrenocorticotropin adenoma Subtypes I and II versus premetastatic tumors (MIB-1 LI and invasiveness); silent adenoma Subtype III versus premetastatic tumors (PCNA and p53 LI); and premetastatic tumors versus metastatic pituitary carcinomas (MIB-1 LI).


CONCLUSIONS
Only trends toward differences were noted between Cushing's versus Nelson's adenomas and between prolactinomas of reproductive female patients versus those of menopausal female patients and male patients. Too few "atypical adenomas" were encountered to permit their comparison with premetastatic tumors, but our results suggest that most pituitary carcinomas arise by malignant transformation from adenomas.
Scheithauer
Bernd W
BW
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. scheithauer.bernd@mayo.edu
Gaffey
Thomas A
TA
Lloyd
Ricardo V
RV
Sebo
Thomas J
TJ
Kovacs
Kalman T
KT
Horvath
Eva
E
Yapicier
Ozlem
O
Young
William F
WF
Meyer
Fredric B
FB
Kuroki
Tamatsu
T
Riehle
Darren L
DL
Laws
Edward R
ER
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear / Q000032:analysis / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis* / Q000503:physiopathology* / Q000601:surgery; D049109:Cell Proliferation; D002648:Child; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018450:Disease Progression; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D009362:Neoplasm Metastasis / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D010902:Pituitary Gland / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D010911:Pituitary Neoplasms / Q000175:diagnosis* / Q000503:physiopathology* / Q000601:surgery; D011003:Ploidies; D011237:Predictive Value of Tests; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000378:metabolism
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; C436291:CDKN1B protein, human; D047908:Intracellular Signaling Peptides and Proteins; C440408:MIB-1 antibody; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27