pS2 is an independent factor of good prognosis in primary breast cancer

Abstract

Summary In breast cancer, oestrogen regulated genes, such as pS2, may be expressed in well differentiated tumours with a good prognosis. We have examined pS2 mRNA expression in 78 primary, untreated breast cancers and related pS2 expression to disease behaviour and known prognostic factors. pS2 mRNA expression was detected in 25/78 (32%) of cancers and was significantly associated with a moderate/high oestrogen receptor content (P = 0.045, Chi Square test). pS2 mRNA expression was associated with freedom from disease at median 31 months clinical and radiological follow-up (P = 0.015, Fisher's exact test, odds ratio 8.6).Using multiple logistic regression analysis of six potential prognostic factors only pathological axillary node status (P<0.01) and pS2 mRNA expression (P<0.05) provided independent prognostic information. Furthermore, pS2 was associated with a good prognosis in the axillary node positive patients where only 1/13 (8%) with pS2 mRNA expression compared with 13/29 (45%) without detectable expression had recurrence of their disease. These data provides strong support for pS2 as a useful independent prognostic factor in primary breast cancer.

PS2 mRNA expression adds prognostic information to node status for 6-year survival in breast cancer

“…pS2 expression was significantly related to oestrogen receptor protein expression as expected for an oestrogen-regulated protein (Rio et al, 1987;Stack et al, 1988;Skilton et al, 1989;Henry et al, 1991;Schwartz et al, 1991;Predine et al, 1992;Thompson et al, 1993;Detre et al, 1994;Foekens et al, 1994;Speiser et al, 1994;Stonelake et al, 1994;Walker et al, 1995;Gibert et al, 1996;Tutschek et al, 1996) and we have confirmed the observations of others that pS2 expression (whether measured as mRNA or protein) is not significantly associated with tumour size or node status (Foekens et al, 1990;Schwartz et al, 1991;Delvenne et al, 1992;Gion et al, 1993).…”

“…The 2-year follow-up on a subgroup of these women forms part of a previous report (Thompson et al, 1993). Patients with impalpable disease or small tumours (when insufficient material was available for study) were excluded from the study.…”

“…Clinical and radiological follow-up (including annual mammography) were continued for at least 6 years or until death; follow-up ranged from 5 to 98 months with a mean followup of 83 months. Total RNA was extracted from snap-frozen tumour tissue using the lithium chloride-urea method, and pS2 expression was determined using the Northern blot technique, with a cDNA probe (Masaikowski et al, 1982) used to detect pS2 messenger ribonucleic acid (mRNA) and actin (Minty et al, 1981) as an internal control for RNA loading (Thompson et al, 1993). Figure 4) and with shorter disease-free interval recurrence and death rates at 6 years.…”

“…The pS2 gene (also known as BCEI, pNR-2, Md2) encodes a 600-base mRNA (Masiakowski et al, 1982), which is translated to a cysteine-rich protein with structural similarities to insulin-like growth factors I and II (Rio et al, 1987;Stack et al, 1988). The clinical interest in pS2 is the result of an association with oestrogen receptor expression and with other conventional markers of good prognosis (Rio et al, 1987;Stack et al, 1988;Schwartz et al, 1991;Predine et al, 1992;Thompson et al, 1993;Detre et al, 1994;Foekens et al, 1994;Speiser et al, 1994;Gibert et al, 1996;Tutschek et al, 1996). pS2 expression is associated with good prognosis in female -but not in male -patients at short-term follow-up (Foekens et al, 1990;Schwartz et al, 1991;Predine et al, 1992;Gion et al, 1993;Kardas et al, 1993;Thompson et al, 1993;Foekens et al, 1994;Speiser et al, 1994).…”

“…The clinical interest in pS2 is the result of an association with oestrogen receptor expression and with other conventional markers of good prognosis (Rio et al, 1987;Stack et al, 1988;Schwartz et al, 1991;Predine et al, 1992;Thompson et al, 1993;Detre et al, 1994;Foekens et al, 1994;Speiser et al, 1994;Gibert et al, 1996;Tutschek et al, 1996). pS2 expression is associated with good prognosis in female -but not in male -patients at short-term follow-up (Foekens et al, 1990;Schwartz et al, 1991;Predine et al, 1992;Gion et al, 1993;Kardas et al, 1993;Thompson et al, 1993;Foekens et al, 1994;Speiser et al, 1994). Conversely, pS2-negative patients have a significantly shorter relapse-free survival (Gion et al, 1993;Foekens et al, 1994;Speiser et al, 1994;Schmidt et al, 1996) and overall survival (Gion et al, 1993;Speiser et al, 1994).…”