Results of immunohistochemical staining of cell-cycle regulators: the prediction of recurrence of functioning pituitary adenoma.
OBJECTIVE
This study was undertaken primarily to investigate the possible prognostic values of several cell-cycle regulators for the prediction of functioning pituitary adenoma (FPA) recurrence after surgical resection by immunohistochemically analyzing tumor samples obtained by surgical resection.


METHODS
The medical records of the patients with FPA diagnosed from January 2000 to December 2009 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center were selected. Immunohistochemical staining was performed on archived paraffin-embedded tissues obtained by surgical resection for adenohypophysial cells, cell-cycle regulatory proteins (p16, p15, p21, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1), MIB-1 antigen, and p53.


RESULTS
Of the 174 FPAs, 62 (35.6%) recurred during follow-up period (mean duration 62.4 months, range 24.2-118.9 months). Immunohistochemically, overstaining for p16 in 89 samples (51.1%), p15 in 27 samples (15.5%), p21 in 20 samples (11.5%), CDK4 in 54 samples (31.0%), CDK6 in 18 samples (10.3%), pRB protein in 69 samples (39.7%), and cyclin D1 in 87 samples (50.0%). Multivariate analysis using the Cox proportional hazard regression model showed that invasion into cavernous sinus (hazard ratio [HR] of 4.02; P < 0.001), immunohistochemical normostaining for p16 (HR of 3.16; P < 0.001), immunohistochemical overstaining for pRB protein (HR of 2.45; P = 0.008), cyclin D1 (HR of 2.13; P = 0.029), MIB-1 antigen (HR of 2.74; P = 0.002), and p53 (HR of 2.21; P = 0.002), predicted the recurrence of FPA after surgical resection.


CONCLUSIONS
Our findings indicate that p16, pRB protein, and cyclin D1 are associated with recurrence FPA after surgical resection.
Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Eun Hee
EH
Lee
Division of Neurooncology, Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Kyu Hong
KH
Kim
Department of Neurosurgery, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, South Korea.
Jae Hyun
JH
Kwon
Department of Neurosurgery, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, South Korea.
Hyung Dong
HD
Kim
Division of Neurooncology, Department of Neurosurgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea. Electronic address: yzkim@skku.edu.
Young Zoon
YZ
Kim
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019938:Cyclin D1 / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D016160:Retinoblastoma Protein / Q000378:metabolism; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
C530104:CCND1 protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; C513496:MIB1 ligase, human; D044767:Ubiquitin-Protein Ligases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6
Cell cycle; Cyclin D1; Pituitary adenoma; RB protein; Recurrence; p16