[Cytosolic pS2 levels in 154 non-small-cell lung carcinomas. Correlation with other clinical and biological parameters].
BACKGROUND
pS2 was first identified as an estrogen induced molecule in a breast cancer cell line, but its gene responds to several growth factors and oncogenic proteins. Its main clinical application lies in breast carcinomas, where it is a molecular marker to identify breast cancer patients who will respond to hormone therapy. This study was performed to evaluate the significance of the pS2 cytosolic levels in non small cell lung carcinomas classified according to different clinical and biological parameters. Likewise, the results obtained were correlated with those observed in normal tissues.


METHODS
The study group included 154 non small cell lung carcinomas (59 adenocarcinomas and 95 squamous carcinomas) and 54 normal lung samples. Cathepsin D, pS2, neuron specific enolase (NSE) and CA125 cytosolic concentrations were determined, as well as those of epidermal growth factor receptor (EGFR), erbB2 protein, CD44s, CD44v5 and CD44v6 on cell surface membranes. Likewise, clinical stage, histological grade, ploidy and cellular S-phase fraction were also considered as variables of the study.


RESULTS
We observed cytosolic pS2 values greater than 1 ng/mg protein (positive cutoff) in 18/59 adenocarcinomas and in 10/95 squamous carcinomas (p:0.00177). In adenocarcinomas, pS2 positivity was not correlated with any clinical and biological parameters, but positive cases had lower EGFR (p:0.03770) concentrations and higher CA125 (p:0.01902) levels. In squamous carcinomas, pS2 positivity was associated with lower EGFR (p:0.02270) levels and higher erbB2 protein (p:0,00563) concentrations.


CONCLUSIONS
Our results led us to suggest the following: 1) cytosolic pS2 concentrations are higher in tumoral than in normal samples; 2) adenoarcinomas had higher levels than squamous lung carcinomas; 3) in adenocarcinomas, positivity for pS2 is associated with lower EGFR levels and higher CA125 concentrations suggesting a worse outcome, and 4) in squamous lung tumors, positivity for pS2 was associated with lower EGFR and higher erbB2 oncoprotein concentrations, it not being possible to establish its clinical significance, although it may be correlated with a poor prognosis.
Ruibal
A
A
Laboratorio de Biología Tumoral FJD, Departamento de Medicina Nuclear, Fundación Jiménez Díaz, Madrid, Spain.
Núñez
M I
MI
del Río
M C
MC
García Díez
S
S
Rodríguez
J
J
Alvarez De Linera
J A
JA
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018394:CA-125 Antigen / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000473:pathology; D002402:Cathepsin D / Q000032:analysis; D003600:Cytosol / Q000737:chemistry*; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000032:analysis; D008175:Lung Neoplasms / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D011506:Proteins / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D016196:S Phase; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D002402:Cathepsin D; D066246:ErbB Receptors; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D011506:Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; C051838:TFF1 protein, human