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Prognostic Markers in Breast Carcinoma

Shilpa Waman Joshi

 

Carcinoma of breast has a relatively high morbidity and mortality rate. This study was done to predict the prognosis of breast carcinomas in relation to oestrogen receptors (OR), progesterone receptors (PR), Cathepsin D, cerb-2 and p53 and to correlate the results with clinical parameters like menopausal status, age and parity in women. Using immunohistochemistry, it was found that the most meaningful correlation was obtained between the hormone receptor status and presence or absence of lymphnodal metastases. A good correlation was also seen with the hormone receptors and menopausal status. As a marker of prognosis Cathepsin D, p53 and cerb-2 were not discriminatory.

 
INTRODUCTION

Mammary cancer is common worldwide and also has relatively high morbidity and mortality , although a large proportion of breast carcinomas are detected early by systematic screening (frequent self examination and mammography). But in India patients present with palpable cancers and even lymphnodal metastases at the time of the first visit. Stratification of patients according to node status and results of ER/ PR receptor analysis has assumed a great therapeutic importance. The object of this study was to correlate the significance of age, menopausal status and parity with the results of ER, PR., cerb-2, p53 and Cathepsin D and to assess the prognosis.

 
Material and Methods

Sixty nine cases of breast carcinoma were selected over a period of one year from the department of Histopathology of Bombay Hospital Institute of Medical Sciences, Mumbai. All paraffin blocks of the tissues and slides and clinical follow up data were available. Immunohistochemistry was carried out in each case. The technique used was based on the labelled streptavidin- biotin [LSAB] method.1 The interpretation of staining was done using positive and negative controls. Presence of a colour product at the site of target antigen [DAB chromogen brown end product] was interpreted as a positive result and absence of staining as a negative result. Only intact cells were examined, avoiding necrotic or haemmorhagic areas.

Staining of cells was assessed semi quantitavely as follows:

(-) No staining
(+) Weak staining
(+ +) Moderate staining
(+ + +) Strong staining

 
Observations
The staining pattern was nuclear in case of ER / PR and p53, cell membrane in cerb-2 and cytoplasmic in Cathepsin D in positive cases. In almost all cases, a crisp reaction end product of moderate to marked intensity was observed. In the group of infiltrating duct and lobular carcinomas the premenopausal women (< 45 years) were 15 in number and postmenopausal (> 45 years) 48 in number. The lymph node status in 4 out of 15 premenopausal women and 12 out of 48 postmenopausal women was not known. 7 out of 11 premenopausal and 19 out of 36 postmenopausal women had lymph nodes metastases. The remaining 6 cases were of uncommon histological type and included 2 medullary, 1 anaplastic, 1 colloid, 1 papillary and 1 neuroendocrine carcinoma. Of these, 2 were in premenopausal women both being carcinomas of medullary type.


Fig. 1 : Distribution of receptors according to menopausal status (n=17).

Fig. 2 :



Fig. 3 : To demonstrate ER/PR status in premenopausal women with positive lymph node metastases (n=7).

Fig. 4 : To demonstrate ER/PR status in postmenopausal women with positive lymph node metastases (n=19).
 
Discussion

The cases were divided into premenopausal and postmenopausal groups, 45 years of age being arbitrarily taken as the outer limit for premenopausal group. The choice of this breakdown was chosen to reflect the fact that most women who were menstruating were < 45 years, whereas those > 45 years either had irregular/ infrequent cycles or no menstruation. It was seen that 64.7% cancers in premenopausal and 40.3% in postmenopausal women were ER / PR-ve, whereas 23.5% cancers in premenopausal and 36.5% in postmenopausal women were ER/ PR+ve (Figs. 1, 2). The higher frequency of ER/ PR receptor positivity in postmenopausal women can be explained on the basis of low levels of circulating oestrogen and progesterone, occurring in this group. These observations agreed with previously published reports.2 The cancers grouped separately showed 2 medullary carcinomas in premenopausal women out of which one was ER/ PR-ve and the other ER/ PR+ve focally. The postmenopausal cases included 1colloid, 1neuroendocrine and 1 papillary carcinoma all of which were positive for ER/ PR receptors. The only cancer negative for ER/ PR in postmenopausal group was the anaplastic type. Cathepsin D, cerb-2 and p53 did not show any significant correlation. Out of the above 69 cases only 2 were nullipara and had ER/ PR-ve cancers, this is similar to that reported by MacMohan et al.3 Histopathological parameter like grade of cancer was found to have no relation with the hormone receptor status. The only significant finding was 85.7% of carcinomas in premenopausal group and 63.15% in postmenopausal group which had nodal metastases were ER/ PR-ve (Figs. 3,4). This proved that carcinomas which were ER/ PR-ve were more likely to metastasize.4


Fig. 5 : LSAB, DAB stain shows positive ER staining of the nuclei (x 100)

Fig. 6 : LSAB, DAB stain shows positive PR staining of the nuclei (x 400)
 

Fig. 7 : LSAB, DAB stain shows positive p53 staining of the nuclei (x 400)

Fig. 8 : LSAB, DAB stain showing characteristic cerb-2 staining along the cell
membranes (x 400)
 
Conclusions

The most meaningful correlation was obtained between the hormone receptor status and presence or absence of lymphnodal metastases. A good correlation was also seen with the hormone receptors and menopausal status. In general, premenopausal women had higher frequency of lymph node metastases as compared to postmenopausal women. As a marker of prognosis Cathepsin D, p53 and cerb-2 were not discriminatory.

 
Acknowledgements
I express my gratitude to my teacher Dr. Arun Chitale, Professor and Head, Department of Pathology, Bombay Hospital institute of Medical Sciences, for his guidance and permitting me to use the data for publication.
 
References
1. Taylor CR. Thereotical and practical aspects of the different immunoperoxidase techniques in immunomicroscopy, 2nd edition, 1994.
2. Pascal Pujol, Pierre Daures. Changing ER and PR patterns in breast carcinoma during menstrual cycle and menopause: Cancer 1998; 83 : 698-705.
3. MacMohan, BCol. Age at first birth and breast cancer risk: WHO, 1970; 43 : 209.
4.
acqueline Ashba. Estrogen and Progesterone receptor concentrations and prevalence of tumor hormonal phenotypes in older breast cancer patients:Cancer detection and prevention, 1990; 23 : 238-244.
   

OUTPATIENT TREATMENT OF ATRIAL FIBRILLATION

Patients with infrequent episodes of atrial fibrillation and only mild heart disease may not be good candidates for prophylactic antiarrhythmic therapy or radiofrequency ablation. Although this approach is effective, it is applicable to only about 10 per cent of patients with episodic atrial fibrillation.

N Engl J Med 2004; 351 : 2384.

NURSES TAKE ON CARDIOVERSION

Nurses can carry out cardioversion in people with atrial fibrillation in a day surgery unit, saving acute hospital beds and junior doctors’ time. Auditing a newly introduced, nurse led electrical cardioversion service in London, Currie and colleagues found that, among 143 patients treated, 92% went back into sinus rhythm. Three had to be admitted to hospital, but for less than 24 hours; none had serious complications. Waiting times were reduced from 27 weeks to eight weeks.

BMJ, 2004; 329 : 892.