Stromal tenascin distribution as a prognostic marker in colorectal cancer

Abstract

Summary A total of 169 colorectal adenocarcinomas, obtained from patients with a median follow-up of 6.5 years, were studied with immunohistochemical staining on cryosections using a monoclonal anti-tenascin antibody to evaluate the possible association between the staining patterns and tumour stage, tumour differentiation and survival. We found two different staining patterns in the tumour stroma -a diffuse stromal fibrillar staining in 92 out of 169 (54%) tumours and a subglandular staining in the remaining 77 tumours. When the entire group of patients (P < 0.01) and the group of potentially cured patients (P < 0.03) were analysed univariately, it was found that diffuse stromal fibrillar staining was associated with a shorter survival time than subglandular staining. In a multivariate analysis, the Dukes' stage and age were independent prognostic factors, whereas the tenascin expression did not retain a clear independent relationship to survival (P = 0.06).Hence, it appears that the tumour expression of tenascin may be a potential prognostic marker in colorectal cancer, in so far as a diffuse stromal fibrillar staining pattern seems to indicate an increased risk of poor outcome. However, after adjustment for age and Dukes' stage, the additional prognostic value of tenascin remains to be established in further analyses.Keywords: tenascin; colorectal cancer; tumour stage; tumour differentiation; survival; immunohistochemistry Tenascin is a large hexameric extracellular matrix protein that is present during embryonic development but essentially absent in normal adult tissues (Schenk and Chiquet-Ehrismann, 1994) and is expressed only at low levels or in a very restricted distribution. Several tenascin isoforms have been described . Tenascin has been suggested to be of importance in the normal healing process and in tumours, in which its role is presumed to be connected with cell adhesion and detachment, cell growth, cell migration and angiogenesis (Mackie et al, 1988;Ekblom and Aufterheide, 1989;Erickson and Bourdon, 1989; ChiquetEhrismann, 1993;Hahn et al, 1995; Joshi et al, 1995). It has been proposed that, although tenascin has no cell adhesion activity, it does affect the cell shape and, thus, may inhibit cell attachment to other extracellular proteins, including fibronectin (Mackie, 1994). It is also thought that tenascin plays a role in coordinating the provisional extracellular matrix surrounding the cancer tissue (Sakakura and Kusakabe, 1994).Several reports have shown an up-regulation of tenascin in various tumour stroma, such as breast (Moch et al, 1993;Shoji et al, 1993;Yoshida et al, 1995), lung (Natali and Zardi, 1989), prostatic (Ibrahim et al, 1993) and gastric carcinomas (Ikeda et al, 1995;Ilunga and Iriyama, 1995). Studies of this putative marker of the tumour matrix are also of considerable interest in colorectal cancer (Sugawara et al, 1991;Riedel et al, 1992;Sakai et al, 1993;Hauptmann et al, 1995;Riedel et al, 1995) because of the potential involvement of tenascin (or tenascin-like proteins) i...

Tenascin-C Expression and Its Prognostic Significance in Colorectal Cancer

“…A diffuse stromal fibrillar staining has been correlated with a poor survival, while a subglandular pattern has been associated with a more favorable prognosis [28, 29]. This finding could not be verified in the present study, since all tumors exhibited a diffuse staining pattern.…”

“…Thus, tenascin-C might support malignant transformation, and already at an early stage, play a detrimental role in tumorigenesis, a role which appears to persist throughout tumor progression [5, 6]. However, in contrast to these cancer-promoting functions, it has been proposed that tenascin-C may also act to prevent tumor invasion and metastasis and consequently confer a better clinical outcome [25, 28, 39, 40]. Tenascin-C is thought to exert a paracrine effect, by which tumor cells force cells in the surrounding stroma to produce a dense desmoplastic fibrous stroma.…”

“…However, high expression of tenascin-C in colorectal cancer has directly or indirectly been correlated with a poor patient prognosis as well [12, 27]. Two distinct stromal staining patterns have been described in colorectal cancer [11, 28, 29], and the distribution of these patterns has been proposed as a prognostic factor, in that a diffuse stromal staining pattern may indicate an increased risk of poor outcome [28, 29]. Further, elevated preoperative serum levels of tenascin-C have been reported to reflect the total tumor burden and to correlate with metastatic disease in colorectal cancer [30].…”

Potencjalne zastosowanie tenascyny C w diagnozowaniu i leczeniu nowotworów

“…Kliniczne znaczenie tenascyny C w nowotworach układu pokarmowego W raku jelita grubego TN-C ulega znacznej ekspresji w zrę-bie otaczającym komórki nowotworowe. U większości przebadanych chorych wykazano zwiększenie ekspresji TN-C w zmianach nowotworowych w porównaniu z normalną śluzówką jelita grubego [73][74][75][76]. Wykazano, że występuje korelacja pomiędzy ekspresją TN-C a gorszym rokowaniem [75] oraz pomiędzy ekspresją mRNA TN-C a zwiększeniem częstości przerzutów do węzłów chłonnych, jak również głębokością inwazji [76].…”

“…U większości przebadanych chorych wykazano zwiększenie ekspresji TN-C w zmianach nowotworowych w porównaniu z normalną śluzówką jelita grubego [73][74][75][76]. Wykazano, że występuje korelacja pomiędzy ekspresją TN-C a gorszym rokowaniem [75] oraz pomiędzy ekspresją mRNA TN-C a zwiększeniem częstości przerzutów do węzłów chłonnych, jak również głębokością inwazji [76]. Przeciwciała przeciwko TN-C mogą być użyteczne do wykrywania raka jelita grubego dzięki powinowactwu do określonych izoform TN-C (przeciwciało J1/tn2 wiąże się z domeną TNfnD w przerzutującym raku jelita grubego, podczas gdy przeciwciało 19H12 wiąże sie z regionem TNfn1,2,4) (tab.…”