Expression of tumor suppressor and tumor-related proteins in differentiated carcinoma, undifferentiated carcinoma with tubular component and pure undifferentiated carcinoma of the stomach.
BACKGROUND
The recent development of tissue microarray (TMA) technology allows high-throughput protein expression profiling of cancer tissues by immunohistochemistry. We attempted to clarify the derivation of undifferentiated-type gastric carcinoma with tubular component by using TMA.


METHODS
We constructed a TMA system composed of six paraffin blocks in which 274 samples of formalin-fixed gastric carcinoma tissue from 274 patients were embedded. Using this system, we performed immunohistochemical stains for five tumor suppressor and tumor-related proteins, i.e. p53, p16, hMLH1, c-erbB-2 and carcinoembryonic antigen (CEA). The 274 gastric carcinomas were histopathologically divided into the following three groups according to the degree of differentiation: differentiated-type (D-type), undifferentiated-type with tubular component (UT-type) and pure undifferentiated-type (UP-type). Immunohistochemical results were then compared with histological types.


RESULTS
The percentages of abnormal expression of each protein in D-type, UT-type and UP-type carcinomas were as follows: 27% (38/143), 17% (17/98) and 15% (5/33) for p53; 27% (39/143), 19% (19/98) and 18% (6/33) for p16; 38% (54/143), 44% (43/98) and 24% (8/33) for hMLH1; 15% (22/143), 5% (5/98) and 0% (0/33) for c-erbB-2; and 22% (31/143), 35% (34/98) and 70% (23/33) for CEA. UP-type carcinomas exhibited the lowest frequencies of abnormal expression for p53, p16, hMLH1 and c-erbB-2, but the highest frequencies for CEA. UT-type carcinomas generally showed intermediate frequencies between those of D-type and UP-type carcinomas. Differences between D-type and UP-type for c-erbB-2 (P < 0.05) and CEA (P < 0.001) were significant, as were differences between D-type and UT-type for c-erbB-2 (P < 0.05) and CEA (P < 0.05), and differences between UT-type and UP-type for hMLH1 (P < 0.05) and CEA (P < 0.001).


CONCLUSIONS
These findings reveal that gastric carcinomas have distinct expression profiles for tumor suppressor and tumor-related proteins depending on histological types, and support the hypothesis that UT-type carcinomas are derived not only from D-type but also from UP-type carcinomas. We also found significant differences between abnormal protein expression and other clinicopathological parameters such as gender, age and status of tumor and nodes.
Honda
Teiichiro
T
Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata 990-9585, Japan.
Tamura
Gen
G
Endoh
Yasushi
Y
Nishizuka
Satoshi
S
Kawata
Sumio
S
Motoyama
Teiichi
T
D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000378:metabolism*; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C501486:MLH1 protein, human