The immunocytochemical detection of axillary micrometastases in breast cancer

Abstract

Summary The histological detection of tumour metastases in axillary lymph nodes from cases of breast carcinoma is of major prognostic significance, but may be difficult when metastases are of microscopic size. We have therefore investigated whether immunohistological techniques can increase the accuracy of metastasis detection in axillary lymph nodes. Forty-five cases of breast carcinoma were studied, in all of whom the axillary lymph nodes had been reported as free of metastases. Paraffin sections from these cases were stained by immunoenzymatic techniques, using monoclonal antibodies directed against human milk fat globule membrane antigen ("anti-EMA") and against epithelial intermediate filaments ("anti-keratin"). In 4/12 cases of lobular carcinoma and in 3/33 cases of ductal carcinoma, previously unsuspected micrometastases were revealed by immunohistological staining, representing an overall increase in detection rate of 15% (and of 33% for the lobular carcinoma cases). In addition to this group of 45 histologically "negative" biopsies, 12 samples were studied in which only a proportion of the nodes had been reported as containing tumour. In 5 of these cases immunostaining revealed previously undetected metastases. These findings suggest that immunohistological analysis may have a routine role to play in the staging of breast carcinoma. It is noted that the 15% increase in diagnostic accuracy achieved in the present study is comparable to the proportion of breast carcinoma patients in whom disseminated disease develops despite their axillary lymph nodes being reported as tumour-free at the time of surgery.

Occult axillary node metastases in breast cancer: their detection and prognostic significance

“…The detection of occult metastases in 25% of cases of ANN breast cancer is higher than that found in most previous studies designed to detect these metastases [Wilkinson et al, 1982;Wells et al, 1984;Trojani et al, 1987a;Raymond and Leong, 1989; International (Ludwig) Breast Cancer Study Group, 1990;Nio et al, 1990;Galea et al, 1991;Byrne et al, 1992;Elson et al, 1993;Hainsworth et al, 1993]. However, the only other study to simultaneously address both sources of error in the standard histopathological technique found metastases in 31% of 159 ANN patients (Nasser et al, 1993).…”

“…Strategies for reducing microscopic misdiagnosis that have been tested include using immunohistochemical techniques to highlight metastases (Wells et al, 1984). More recently, a technique using reverse transcriptase-polymerase chain reaction (RT-PCR) to detect expression of tumour-associated antigen mRNA extracted from axillary nodes has been tested as an alternative to histopathological examination (Noguchi et al, 1994).…”

“…For example, in a Ludwig Breast Cancer Study Group examination of lymph nodes from 921 patients using a laborious serial sectioning procedure examining 36 sections from each block, only 9% of patients were found to have metastases [International (Ludwig) Breast Cancer Study Group, 1990]. This proportion is equal to or less than that found by many trials using a more practical strategy of immunohistochemical detection in a single section (Wells et al, 1984;Trojani et al, 1987a;Raymond and Leong, 1989;Galea et al, 1991;Byrne et al, 1992;Elson et al, 1993; Hainsworth et al, 1993). Despite its apparently high detection rate, immunohistochemical detection in a single section ignores the reality of sampling error.…”

Micrometastases to axillary lymph nodes from carcinoma of breast: Detection by immunohistochemistry and prognostic significance

“…Several laboratories have recently used these techniques to detect such micrometastases either in bone marrow (Redding et al, 1983) or in lymph nodes (Sloane et al, 1980;Wells et al, 1984 (21%) were postoperatively irradiated and 9 (6%) received a brief course of chemotherapy. All slides of tumours and lymph nodes were reviewed to determine histologic tumour type (WHO 1981) grading (Scarff-Bloom) and lymphatic invasion.…”

Prognostic significance of occult lymph node micrometastasis in gastric cancer: a histochemical and immunohistochemical study based on 1997 UICC TNM and 1998 JGCA classifications

“…These may be due at least in part to the presence of lymph node micrometastasis at the time of resection. Although it is not consensual, micrometastasis can be defined as one single cell or a cluster of malignant cells inside of the lymph node that are not visualized by routine methods, but only by special dies, as immunohistochemical AE1-AE3 techniqu es 1,4,6,11,18,29,33,35,36,38 . In order to clarify this issue we studied 28 patients prospectively, treated by radical surgery, minimum of 30 lymph nodes resected from D2 lymphadenectomy and 43 lymph nodes from modified D3 lymphadenectomy.…”