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Association of int2/hst1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis

Borg, A. LU ; Sigurdsson, H.; Clark, G. M.; Ferno, M. LU ; Fuqua, S. A.W.; Olsson, H. LU ; Killander, D. LU and McGurie, W. L. (1991) In British Journal of Cancer 63(1). p.136-142
Abstract

The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome llql3 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the... (More)

The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome llql3 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0. 001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HSTI amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0. 015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 1 lql3 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at llql3 is due to the activity of INT2, HSTl or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Cancer
volume
63
issue
1
pages
136 - 142
publisher
Nature Publishing Group
external identifiers
  • scopus:0026057931
ISSN
0007-0920
DOI
10.1038/bjc.1991.28
language
English
LU publication?
yes
id
29452eea-6821-4d54-80aa-381f96c8ef10
date added to LUP
2018-12-19 14:48:59
date last changed
2019-03-08 03:13:10
@article{29452eea-6821-4d54-80aa-381f96c8ef10,
  abstract     = {<p>The human proto-oncogene INT2 (homologous to the mouse INT2 gene, implicated in proviral induced mammary carcinoma) has been mapped to chromosome llql3 and found to share band localisation with, among others, the HST1 proto-oncogene. Both genes are members of the fibroblast growth factor family. In the present study, coamplification (2-15 copies) of the INT2/HST1 genes was found in 27 (9%) of 311 invasive human breast carcinomas using slot blot and Southern blot analyses. Amplification was not correlated to tumour size, axillary lymph node status or stage of disease, neither to patient age nor menopausal status. However, 26 (96%) of the 27 amplified tumours were, often strongly, Oestrogen receptor positive compared to 65% of the unamplified cases (P = 0. 001). These findings are in sharp contrast to the strong correlations of HER-2/neu proto-oncogene amplification with advanced stage and steroid receptor negativity, previously observed in the same series of tumours. Patients with INT2/HSTI amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0. 015, median follow up 45 months). This correlation was confined to node-negative patients and persisted in multivariate analysis. No significant correlation to survival from breast cancer was found. It is concluded that amplification of the 1 lql3 region in breast cancer occurs in a particular subset of aggressive tumours, quite different from that identified by HER-2/neu amplification. It still remains to be shown that the selection for amplified genes at llql3 is due to the activity of INT2, HSTl or yet another, still unidentified, neighbouring gene. However, the results are potentially of clinical value in separating a group of node-negative breast cancer for more intense treatment.</p>},
  author       = {Borg, A. and Sigurdsson, H. and Clark, G. M. and Ferno, M. and Fuqua, S. A.W. and Olsson, H. and Killander, D. and McGurie, W. L.},
  issn         = {0007-0920},
  language     = {eng},
  month        = {01},
  number       = {1},
  pages        = {136--142},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Association of int2/hst1 coamplification in primary breast cancer with hormone-dependent phenotype and poor prognosis},
  url          = {http://dx.doi.org/10.1038/bjc.1991.28},
  volume       = {63},
  year         = {1991},
}