The potential role of TGFbeta1, TGFbeta2 and TGFbeta3 protein expression in colorectal carcinomas. Correlation with classic histopathologic factors and patient survival.
OBJECTIVE
This study investigates the expression of tumor growth factors TGFbeta1, TGFbeta2 and TGFbeta3 in tissue material from patients with colorectal carcinoma and evaluates their correlation with known prognostic markers and patient survival.


METHODS
The study included 124 patients with colorectal carcinoma. According to the TNM classification of malignant tumors, 26 tumors were identified as being stage I, 30 stage II, 48 stage III, and 20 stage IV, whereas 106 tumors were low-grade and 18 high-grade malignancies. On paraffin sections, the streptavidin-biotin technique using antibodies against TGFbeta1, TGFbeta2 and TGFbeta3 was applied. Morphological and immunohistochemical results were correlated with clinicopathologic parameters.


RESULTS
TGFbeta1 protein was expressed in 88 out of 124 (71%) carcinomas, whereas TGFbeta2 and TGFbeta3 proteins were detected in all tumors examined. Normal colonic mucosal epithelial cells expressed TGFbeta2 (significantly less as compared to neoplastic cells; p < 0.01) and TGFbeta3 (p > 0.05 compared to neoplastic cells), but not TGFbeta1. Statistical analysis revealed a higher expression of TGFbeta1 in low-grade carcinomas (p = 0.009) and a higher presence of TGFbeta2 in advanced tumors (p = 0.008). TGFbeta1 expression was related with increased disease-free and overall survival (p < 0.05 each). The presence of TGFbeta2 was correlated with worse prognosis (p < 0.05). Cox analysis revealed that besides tumor grade and stage, TGFbeta1 expression constituted an independent prognostic factor.


CONCLUSIONS
This study shows that in adenocarcinomas of the colon, there is a differential expression of TGFbeta1, TGFbeta2 and TGF3. TGFbeta1 may be implicated in the pathogenesis of these tumors, since it is expressed only in neoplastic but not in normal cells. TGFbeta1 is related with an increased disease-free and overall survival and constitutes an independent prognostic factor. In advanced stages, TGFbeta2 seems to be involved in tumor progression and is related with worse prognosis.
Tsamandas
Athanassios C
AC
Department of Pathology, University of Patras School of Medicine, Patras, Greece.
Kardamakis
Dimitrios
D
Ravazoula
Panagiota
P
Zolota
Vassiliki
V
Salakou
Stavroula
S
Tepetes
Konstantinos
K
Kalogeropoulou
Cristina
C
Tsota
Irene
I
Kourelis
Theodore
T
Makatsoris
Thomas
T
Karavias
Dionissios
D
Scopa
Chrisoula D
CD
Bonikos
Dionysis S
DS
Kalofonos
Haralambos P
HP
Petsas
Theodore
T
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D003106:Colon / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011182:Postoperative Care; D011379:Prognosis; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012007:Rectum / Q000473:pathology; D016019:Survival Analysis; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000502:physiology
D000964:Antimetabolites, Antineoplastic; D016212:Transforming Growth Factor beta; D002955:Leucovorin; D005472:Fluorouracil