Assessment of proliferative activity in carcinomas of the human alimentary tract by Ki‐67 immunostaining

Summary Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus were investigated immunohistochemically with the monoclonal antibody MIB-I, which recognises proliferating cells. Using light microscopy, the number of MIB-I-positive tumour cells was counted in the areas with the highest proliferative activity. The MIB-1 index was determined as the proportion of MIB-I-positive and MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was found between the different tumours with a minimum of 6% and a maximum of 95% (median, 33%). The MIB-1 index correlated significantly with the mitotic activity in the tumour tissue (r =0.33; P=0.0001) and with the proportion of apoptotic tumour cells (r=0.25; P=0.0017). No significant correlation was found between the MIB-1 index and various other prognostic parameters including pT classification, pN classification, tumour size, tumour grade, blood vessel invasion and lymphatic vessel invasion. In the univariate survival analysis no significant difference was found between tumours with low (<33%) and high MIB-1 index (>33%) (5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%). In a Cox proportional hazard regression analysis only the parameters lymphatic vessel invasion (P=0.0001), pT classification (P=0.0034) and pN classification (P=0.0256), but not the MIB-1 index, could be verified as independent prognostic variables. In conclusion, evaluation of the MIB-1 index does not provide prognostic information for oesophageal cancer patients.

Section: Materials and Methods Patientssupporting

confidence: 92%

The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus

Sarbia

Bittinger²,

Porschen³

et al. 1996

“…In both of these studies, using the PCNA antibody, the intestinal-type carcinomas also had a higher growth fraction than the diffuse-type carcinomas, although the difference did not reach statistical significance. Furthermore, it was shown that in experimentally induced colon carcinomas also, the undifferentiated tumours exhibited a statistically significant lower tumour cell proliferation than differentiated gland-building tumours (Gabbert et al, 1982 findings are in accordance with those of some other studies using Ki-67 (Yonemura et al, 1990a;b, 1991), a positive correlation between a high PI and pT category was also reported using Ki-67 (Kakeji et al, 1991) or PCNA (Mori et al, 1993;Yonemura et al, 1993), whereas Jain et al (1991) reported a higher tumour cell proliferation index in lower pT categories using PCNA. In our study a statistically significant correlation was found between tumour cell proliferation at the invasion front and the presence of blood or lymphatic vessel invasion, which has been shown in the same population of patients to be important prognostic factors in gastric carcinomas (Gabbert et al, 1991).…”

Section: Discussionsupporting

confidence: 69%

“…Concerning the correlation of tumour cell proliferation with clinicopathological parameters, contradictory results have been reported in gastric cancer using either Ki-67 (Yonemura et al, 1990a, b, 1991Kakeji et al, 1991;Porschen et al, 1991) or PCNA (Jain et al, 1991;Mori et al, 1993;Yonemura et al, 1993;Maeda et al, 1995). In the present study we were able to show a statistically significant correlation between tumour cell proliferation and histological tumour type according to the Lauren classification.…”

Section: Discussionmentioning

confidence: 99%

“…Investigations on tumour cell proliferation have also been carried out in gastric cancer (Yonemura et al, 1990a(Yonemura et al, ,b, 1991(Yonemura et al, , 1993Porschen et al, 1991;Jain et al, 1991;Kakeji et al, 1991;Mori et al, 1993), only some of which have also focused on its prognostic role. Whereas Yonemura et al (1990a) as well as Mori et al (1993) stressed the proliferative activity as an independent prognostic parameter in gastric cancer, Jain et al (1991) failed to show this correlation.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical study on the prognostic value of MIB-1 in gastric carcinoma

Müller

Schneiders²,

Meier³

et al. 1996

Summary The prognostic significance of tumour cell proliferation was investigated in a series of 418 gastric carcinomas using the monoclonal antibody MIB-1. Owing to strong intratumoural heterogeneity of MIB-1 expression three different proliferation indices (PIs) were determined in all carcinomas: (1) PImax in areas of maximal tumour cell proliferation, (2) PIrand in areas randomly distributed over the whole tumour, (3) Plfront in areas exclusively located at the tumour invasion front. There was a strong intertumoral heterogeneity with

“…Ki-67 immunoreactivity has been studied in several types of carcinoma, e.g. in breast carcinoma (Barnard et al, 1987;Gasparini et al, 1992;Locker et al, 1992), in bladder carcinoma (Fontana et al, 1992), in carcinoma of the prostate (Thompson et al, 1992) and in colon carcinoma (Porschen et al, 1991 Tissue preparation The breast specimens were laid on ice and frozen in liquid nitrogen within 45 min. Sections for Ki-67 labelling, were stored at -20°.…”

mentioning

confidence: 99%

Prognostic value of Ki-67 immunolabelling in primary operable breast cancer

Railo

Nordling²,

Boguslawsky³

et al. 1993

Summary The prognostic value of Ki-67 immunohistochemical labelling was evaluated in 327 operable primary carcinomas of the breast. The follow-up time was up to 4 years (mean 2.7 years). The disease-free survival in Ki-67 positive patients was shorter than in Ki-67 negative patients (P<0.005). By combining the Ki-67 expression with ER receptors and stage, subgroups with a different disease-free survival were identified. In stage II patients there was a significant difference (P <0.005) in disease-free survival between Ki-67 positive/ER negative and Ki-67 negative/ER positive patients. In node negative patients there was no such difference. The disease-free survival according to different prognostic factors, stage, ER and node status, were separately examined using a Cox's proportional hazards model. ER (P <0.0001), the Ki-67 (P <0.02), tumour size (P<0.0001) and nodal status (P<0.006) were independent prognostic factors. We conclude that the potential value of Ki-67 labelling for prognostic evaluation of patients with breast carcinoma is good.The increasing number of options for the treatment of breast carcinoma has made the prognostic evaluation of the disease even more important. The histologic criteria for grading of the carcinoma into poorly differentiated and well differentiated ones was established already in 1957 (Bloom & Richardson, 1957). Patients with poorly differentiated tumours have a shorter relapse-free survival than those with differentiated ones. Node positivity also decreases the disease-free survival time (Du-Toit et al., 1990;Fisher et al., 1983). Methods of 3H Thymidine incorporation (Silvestrini et al., 1974) and flow cytometry (Kallioniemi et al., 1987) are well established but complex procedures giving prognostic information. It is desirable to find easier methods for the prognostic evaluation of breast carcinoma. In this respect the introduction of a mouse monoclonal antibody Ki-67 by Gerdes et al. (1983) simplified the measurement of proliferative activity in breast carcinoma tissue. The monoclonal antibody labels a still unknown nuclear antigen in proliferating cells. Cell nuclei in the resting stage (GO) are not stained. Ki-67 immunoreactivity has been studied in several types of carcinoma, e.g. in breast carcinoma (Barnard et al., 1987;Gasparini et al., 1992;Locker et al., 1992), in bladder carcinoma (Fontana et al., 1992), in carcinoma of the prostate (Thompson et al., 1992) and in colon carcinoma (Porschen et al., 1991 Tissue preparation The breast specimens were laid on ice and frozen in liquid nitrogen within 45 min. Sections for Ki-67 labelling, were stored at -20°. The acetone-fixed, air-dried sections were incubated for 60 min at room temperature with the primary Ki-67-antiserum (DakopattsO) diluted 1:10. The rest of the staining procedure was performed using the avidin-biotin method (ABC-Kit, Vector Laboratories@, Burlingame, California). The result was visualised using AEC as chromogen. Finally the sections were lightly counterstained with Mayer's haematoxylin. For the immu...