1: Geburtshilfe Frauenheilkd. 1996 Apr;56(4):177-83. 

[Value of immunohistochemical determination of receptors, tissue proteases,
tumor suppressor proteins and proliferation markers as prognostic indicators in
primary breast carcinoma]

[Article in German]

Gohring UJ, Scharl A, Ahr A.

Klinik und Poliklinik fur Frauenheilkunde und Geburtshilfe, Universitt Koln.

OBJECTIVE: We tested whether immunohistochemical detection of oestrogen and
progesterone receptor (ER, PR), the oestrogen-dependent protein pS2, the growth
hormone receptors p 185neu and EGF-R, the tumour suppressor protein p53, the
tissue proteases Cathepsin D and Urokinase, and the proliferation marker PCNA
are of prognostic relevance in breast cancer patients. METHODS: Expression of
the proteins listed above was evaluated in formalin-fixed and paraffin-embedded
sections of 311 primary breast cancer specimens using modified
Avidin-Biotin-Complex methods. Results were correlated to clinical and
morphological parameters (age, menopausal status, nodal status, tumour size,
tumour grade), and clinical course of disease (complete follow-up in 301 women,
median observation time 62 months) utilising univariate and multivariate
statistical analyses. RESULTS: If univariate analyses and multivariate
regression analyses according to the Cox-model were applied, only Cathepsin D
correlated to an elevated risk for recurrence in nodally negative patients (n =
135). In nodally positive women (n = 161), increasing tumour size, tumour grade,
lack of ER and PR, expression of p185neu, p53, and PCNA indicated a
significantly increased relative risk. CONCLUSIONS: Immunohistochemistry allows
the detection of parameters which may indicate prognosis in subgroup of breast
cancer patients.

PMID: 8682282 [PubMed - indexed for MEDLINE]


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2: Anticancer Res. 1996 Mar-Apr;16(2):1011-8. 

Comparative prognostic value of Cathepsin D and urokinase plasminogen activator,
detected by immunohistochemistry, in primary breast carcinoma.

Gohring UJ, Scharl A, Thelen U, Ahr A, Crombach G.

Department of Obstetrics, University of Cologne, Germany.

The lysosomal protease Cathepsin D and the serine protease urokinase plasminogen
activator (uPA) are suspected to indicate poor prognosis in primary breast
carcinoma. We tested Cathepsin D and uPA immunohistochemically in 281 surgical
specimens of primary ductal infiltrating breast carcinomas. Staining was
evaluated, taking intracytoplasmic immunoreactions into account, in tumour cells
and tumour infiltrating macrophages. Positivity was established in 48.4% and
58.0% of tissue samples for cathepsin D and uPA respectively (co-expression:
67.6%). In patients with cathepsin D- or uPA-positive tumours, relapses were
more frequent and disease-free survival was shorter irrespective of nodal
status, receptor status or menopausal status, (median observation time 74
months). However, this trend was statistically significant only for cathepsin D.
With stepwise cox regression analysis, borderline significance (p = 0.07) was
calculated for cathepsin D only in node-negative patients. The combination of
cathepsin D with uPA measurements did not enhance its prognostic value.
Immunohistochemical detection of Cathepsin D could potentially be used to
identify patients with poor prognosis in the group of node negative breast
cancer patients.

PMID: 8687092 [PubMed - indexed for MEDLINE]


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3: Pathologe. 1995 Nov;16(6):398-403. 

[Prognostic value of immunohistochemical determination of urokinase plasminogen
activator in primary breast cancers]

[Article in German]

Gohring UJ, Scharl A, Thelen U, Ahr A, Titius BR.

Klinik und Poliklinik fur Frauenheilkunde und Geburshilfe, Universitat zu Koln.

There is ample evidence that the protease urokinase plasminogen activator (uPA)
plays a role in invasion and spread of tumours. Several publications suggest its
biochemical measurement in tumour cytosols to be of prognostic significance in
breast carcinomas. Our study set out to determine whether the
immunohistochemical detection of uPA in formalin-fixed, paraffin-embedded
primary breast cancer tissues is of prognostic relevance. We tested 269 surgical
specimens of primary ductal infiltrating carcinoma immunohistochemically using a
modified avidin-biotin method. Some 57% of carcinoma specimens yielded specific
positive staining in tumour cells. Detection of uPA correlated to tumour grade
(P = 0.04), and to the detected level of the proliferation marker PCNA (P =
0.002), but not to patients' age or menopausal status, tumour size, nodal or
steroid receptor status (P > 0.05). At median 68 months' follow-up, 34% of
patients had experienced tumour relapse and 28% had died from cancer. Clinical
course was correlated significantly to tumour size, tumour grade, nodal and
steroid hormone receptor status (P < 0.05). Immunohistochemical detection of
uPA, however, could not be demonstrated to be of any prognostic significance
with regard to relapse-free or overall survival (P > 0.05) in the total study
group or in the N0 (n = 120) and N + (n = 144) subgroups, regardless of whether
univariate or multivariate analysis was applied.

PMID: 8570558 [PubMed - indexed for MEDLINE]


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