Prognostic relevance of cathepsin D versus oestrogen receptors in node negative breast cancers

Granata, G.; Coradini, Danila; Cappelleti, V.; Fronzo, G. Di

doi:10.1016/0277-5379(91)90260-k

Cited by 48 publications

(21 citation statements)

References 7 publications

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“…There was also a weak association of Cath D with both ER and PgR, as already found in several studies (Cazin et al, 1993;Gion et al, 1995), but not all (Granata et al, 1991). This study also confirmed the association of high Cath D level with SBR grade II and III previously reported (Cazin et al, 1993;Gion et al, 1995), as well as its correlation to pS2 (Gion et al, 1995).…”

Section: Discussionsupporting

confidence: 90%

Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer

Pujol

et al. 1999

Br J Cancer

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Many studies have addressed the clinical value of pS2 as a marker of hormone responsiveness and of cathepsin D (Cath D) as a prognostic factor in breast cancer. Because pS2 and Cath D are both oestrogen induced in human breast cancer cell lines, we studied the influence of the menstrual cycle phase and menopausal status at the time of surgery on the levels of these proteins in breast cancer. A population of 1750 patients with breast cancer, including 339 women in menstrual cycle, was analysed. Tumoral Cath D and pS2 were measured by radioimmunoassay. Serum oestradiol (E2), progesterone (Pg), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels at the day of surgery were used to define the hormonal phase in premenopausal women. There was a trend towards a higher mean pS2 level in the follicular phase compared with the luteal phase (17 ng mg −1 and 11 ng mg −1 respectively, P = 0.09). Mean pS2 was lower in menopausal patients than in women with cycle (8 ng mg −1 and 14 ng mg −1 respectively, P = 0.0001). No differences in mean Cath D level were observed between the different phases of the menstrual cycle, or between pre- and post-menopausal women. In the overall population, pS2 was slightly positively associated with E2 and Pg levels and negatively associated with FSH and LH, probably reflecting the link between pS2 and menopausal status. In premenopausal women, no association was found between pS2 and E2, Pg, FSH or LH levels. There were no correlations between Cath D level and circulating hormone levels in the overall population. However, in the subgroup of premenopausal women with ER-positive (ER+) tumours, E2 was slightly associated with both pS2 and Cath D, consistent with oestrogen induction of these proteins in ER+ breast cancer cell lines. There are changes in pS2 level in breast cancer throughout the menstrual cycle and menopause. This suggests that the choice of the pS2 cut-off level should take the hormonal status at the time of surgery into account. In contrast, the level of Cath D is unrelated to the menstrual cycle and menopausal status. 1999 Cancer Research Campaign

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Section: Discussionsupporting

confidence: 90%

Time at surgery during menstrual cycle and menopause affects pS2 but not cathepsin D levels in breast cancer

Pujol

et al. 1999

Br J Cancer

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“…Similar results for early relapses in node negative patients have been obtained with her/neu oncogene (Slamon & Clark, 1988). Cathepsin D has also failed to predict disease-free survival in node negative patients, while its predictive value was considerably strengthened when combined with ER-determinations (Granata et al, 1991). Long term follow-up studies on stage I and node negative patients show that a recurrence can occur decades after the initial diagnosis.…”

Section: Discussionsupporting

confidence: 57%

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

Railo

Nordling²,

Boguslawsky³

et al. 1993

Br J Cancer

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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...

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“…Oestrogen regulated genes are ideal candidates and we have previously described the cloning of eleven such genes (2-4). However, we and others (8, 14), have found that many genes originally isolated as oestrogen responsive in cell culture, fail to maintain this responsiveness in tumours where their expression is not correlated to ER status (14). It therefore appears likely that for the majority of oestrogen responsive genes the steroidal regulatory component can be circumvented by other stimulatory mechanisms.…”

Section: Discussionmentioning

confidence: 81%