Histologic-type specific role of cell cycle regulators in non-small cell lung carcinoma.
BACKGROUND
Lung cancer is the most lethal type of cancer in humans. Cell cycle alterations have commonly been encountered in lung cancer and may have prognostic value.


METHODS
This study investigates the immunohistochemical expression of the important cell cycle regulators phosphatase and tensin homolog deleted on chromosome 10 (PTEN), p27, Cks1, and Skp2 in 128 non-small cell lung carcinomas (64 adenocarcinomas, 46 squamous cell carcinomas, and 18 large cell undifferentiated carcinomas) and adjacent non-neoplastic lung tissue.


RESULTS
PTEN and p27 were always highly expressed in non-neoplastic lung whereas Cks1 and Skp2 were not expressed in normal tissue. Decreased PTEN expression was noted in 19/64 adenocarcinomas, 15/46 squamous cell carcinomas, and 7/18 undifferentiated large cell carcinomas. Reduced expression of p27 was noted in 28/64, 19/46, and 6/18 of the tumors, respectively. Increased expression of Cks1 was seen in 38/64, 26/46, and 11/18 and increased expression of Skp2 in 29/64, 30/46, and 14/18 of the tumors, respectively. An inverse relationship between p27 and Skp2 levels was found in adenocarcinomas and between p27 and Cks1 levels in squamous cell carcinomas. Decreased PTEN and p27 expression were associated with advanced tumor stage in squamous cell carcinomas. Univariate analysis showed that high p27 and PTEN and low Cks1 expression correlated with increased survival in patients with squamous cell carcinoma independently of tumor stage.


CONCLUSIONS
Aberrant expression of PTEN, p27, Cks1, and Skp2 is a common feature of all three major types of non-small cell lung cancer NSCLC, but seems to be involved in the progression of squamous cell carcinoma alone.
Zolota
Vassiliki G
VG
Department of Pathology, Medical School, University of Patras, Patras, Greece. zol@med.upatras.gr
Tzelepi
Vassiliki N
VN
Leotsinidis
Michael
M
Zili
Paraskevi E
PE
Panagopoulos
Nikolaos D
ND
Dougenis
Demetrios
D
Tsamandas
Athanassios C
AC
Scopa
Chrisoula D
CD
D000230:Adenocarcinoma / Q000145:classification / Q000235:genetics / Q000473:pathology / Q000601:surgery; D042846:CDC2-CDC28 Kinases; D002289:Carcinoma, Non-Small-Cell Lung / Q000145:classification / Q000235:genetics / Q000473:pathology* / Q000601:surgery*; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000235:genetics / Q000473:pathology / Q000601:surgery; D002352:Carrier Proteins / Q000235:genetics; D002453:Cell Cycle; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology* / Q000601:surgery*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics
C093090:CKS1B protein, human; D002352:Carrier Proteins; D018809:Proliferating Cell Nuclear Antigen; D044786:S-Phase Kinase-Associated Proteins; C413374:p27 antigen; D042846:CDC2-CDC28 Kinases; D018844:Cyclin-Dependent Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human