Clinicopathologic features, cellular differentiation, PCNA and P53 expressions in gastrointestinal stromal tumors.
OBJECTIVE
Gastrointestinal stromal tumors are currently defined, as specific c-kit positive primary mesenchymal tumors of the gastrointestinal tract. Although increasing tumor size and mitotic activity favours aggressive behaviour, no specific histological criteria that enable the prediction of biological behaviour have yet been identified. The purpose of this study is, (1) to determine whether cell differentiation of gastrointestinal stromal tumors could be detected through their expression of various antigens, (2) to correlate their macroscopic and histologic features with cell differentiation, p53 expression, PCNA score and clinical outcome.


METHODS
65 gastrointestinal stromal tumors were included in this study. All cases were reviewed in terms of clinical presentation and courses. The cell morphology, growth pattern, cellularity, pleomorphism, mucosal invasion, necrosis and mitotic index were evaluated. Tissue sections were immunostained with CD117, CD34, alpha-smooth muscle actin, and S-100 protein. PCNA score and p53 expressions were investigated to determine whether these could be used as prognostic indicator.


RESULTS
Clinical outcome was obtained for 42 of the 65 patients. The follow-up time ranged from 1 to 240 months (median: 20 months). The tumors occurred in 34 female and 31 male patients, ranging in age from 1.5 months to 80 years (median: 53 years). Tumors were located in the stomach (19), duodenum (10), jejunum and ileum (19), the colon (5), the anorectal region (5) and in the mesentery or omentum (7). 55 tumors had spindle, 7 showed spindle and epithelioid, 3 had pure epithelioid morphology. Mitotic rate was found significantly different between probably benign 11 cases and recurrent 11 and metastatic 25 cases (p=0.001). Immunohistochemically, CD117 positivity was found 52 tumors (80%). 4 of 13 CD117 negative tumors were positive for CD34. 4 of 9 tumors showing were also a-SMA and S-100 negative. CD34 positivity was determinated in 44 tumors (67.6%). alpha-SMA reactivity was seen in 39 tumors (60%). Only 5 tumors showed S-100 protein reactivity (7.69%). Statistically, mitotic rate was found significantly different between probably benign 11 cases and recurrent 11 and metastatic 14 cases (p=0.001). Furthermore, there were significant differences between the probably benign neoplasms and recurrent or metastatic cases in following parameters; p53 expression, PCNA score, presence of necrosis and cellularity.


CONCLUSIONS
GISTs could be specifically differentiated neoplasms and their some other aspects should be clarified such as relations with c-kit and other oncogenes and dual or "null" differentiation in the same neoplasm.
Can
Bilge
B
Sökmensüer
Cenk
C
D000199:Actins / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D015999:Multivariate Analysis; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D009336:Necrosis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000199:Actins; D018952:Antigens, CD34; D018809:Proliferating Cell Nuclear Antigen; D009418:S100 Proteins; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit