Role of immunohistochemical detection of lymph-node metastases in management of breast cancer

doi:10.1016/S0140-6736(98)11104-2

The Lancet

Volume 354, Issue 9182, 11 September 1999, Pages 896-900

https://doi.org/10.1016/S0140-6736(98)11104-2 Get rights and content

Summary

Background

This study was designed to ascertain whether immunohistochemical methods could improve the detection of metastases in primary breast cancer patients whose axillary lymph nodes were classified, by conventional methods, as disease free.

Methods

Ipsilateral lymph nodes (negative for metastases by routine histology) from 736 patients (participants in Trial V of the International [Ludwig] Breast Cancer Study) were examined by serial sectioning and staining with haematoxylin and eosin (two sections from each of six levels) and by immunohistochemistry of a single section (with two anticytokeratins AE-1 and CAM 5·2). After median follow-up of 12 years, disease-free and overall survival were estimated by Kaplan-Meier methods.

Findings

Occult nodal metastases were detected by serial sectioning and haematoxylin and eosin in 52 (7%) of 736 patients and by immunohistochemistry in 148 (20%). Only two (3%) of 64 invasive lobular or mixed invasive lobular and ductal cancers had node micrometastases, detected by haematoxylin and eosin, compared with 25 (39%) by immunohistochemistry. Occult metastases, detected by either method, were associated with significantly poor disease-free and overall survival in postmenopausal but not in premenopausal patients. Immunohistochemically detected occult lymph-node metastases remained an independent and highly significant predictor of recurrence even after control for tumour grade, tumour size, oestrogen-receptor status, vascular invasion, and treatment assignment (hazard ratio 1·79 [95% CI 1·17–2·74], p=0·007).

Interpretation

The immunohistochemical examination of ipsilateral axillary lymph nodes is a reliable, prognostically valuable, and simple method for the detection of occult nodal metastases. Immunohistochemistry is recommended as a standard method of node examination in postmenopausal patients.

Introduction

The most important prognostic factor in patients with breast cancer is the presence of axillary lymph-node metastases.1, 2 About 25% of patients who are node-negative by standard histopathological criteria will develop distant metastases.¹ Adjuvant chemotherapy benefits some patients with node-negative breast cancer³ but treatment of all node-negative patients is unnecessary, since most node-negative patients will never have recurrence after surgery. There is, therefore, a clear need to identify patients with node-negative breast cancer who are at increased risk of disease progression, or in whom this has already occurred but is as yet occult, because this group may benefit most from adjuvant systemic therapy. Similarly, patients who do not require systemic therapy after surgery should also be identified (ie, patients whose tumours have not metastasised), sparing them from the side-effects of adjuvant chemotherapy as well as the expense of such treatment.

The International (Ludwig) Breast Cancer Study Group reported, in 1990, on their analysis of 921 patients with breast cancer and histologically negative ipsilateral axillary lymph nodes.⁴ Histological review of serial sections of lymph nodes at many levels, yielded 83 cases (9%) with occult metastases. The study reported unequivocally that the presence of occult lymph-node metastases was significantly associated with earlier time to recurrence and decreased survival. However, the protocol was impractical, since on average 144 slides per patient had to be histologically examined.

The purpose of this study, which is based on the same population of patients as the previous trial, was to find out whether immunohistochemical methods can be used to detect occult nodal metastases reliably, to identify patients with occult nodal breast-cancer metastases, and to ascertain whether this population was more likely to develop metastatic disease.

Section snippets

Methods

Full details of all the patients who took part in the multicentre International (Ludwig) Breast Cancer Study Group Trial V have been reported previously,³ as have the histopathological methods used to search for the presence or absence of axillary lymph-nodes metastases.⁴

All the histological material, including the primary tumours, was assessed by the Central Review Pathology Panel, and the following data were recorded: tumour size, histological tumour type, tumour grade, and presence or

Results

Of the 736 patients studied, 52 (7%) had occult lymph-node metastases detected on serial sections stained with haematoxylin and eosin. By contrast, 148 (20%) had occult metastases detected by immunohistochemical methods on a single section (table 1). In 626 (85%) cases, the results of the two assay methods were the same; 45 (6%) cases were positive by both methods and 581 (79%) were negative by both methods. Among the 110 cases for which there was disagreement, significantly more cases were

Discussion

When examining breast carcinomas and related material, the pathologist aims to achieve, as simply and reliably as possible, a comprehensive diagnosis and prognosis with therapeutic relevance. The results of this study indicate an advance towards the better assessment of axillary lymph-node status through the use of immunohistochemistry.

This approach could help to improve the sensitivity of detection of metastases in staging and therapy, particularly when little tissue is available as is the

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With more than 60,000 new cases of breast cancer in mainland France in 2023 and 8% of all cancer deaths, breast cancer is the leading cancer in women in terms of incidence and mortality. While the number of new cases has almost doubled in 30 years, the percentage of patients at all stages alive at 5 years (87%) and 10 years (76%) testifies to the major progress made in terms of screening, characterisation and treatment. However, this progress, rapid as it is, needs to be evaluated and integrated into an overall strategy, taking into account the characteristics of the disease (stage and biology), as well as those of the patients being treated. These are the objectives of the St Paul-de-Vence recommendations for clinical practice. We report here the summary of the votes, discussions and conclusions of the Saint-Paul-de-Vence 2022-2023 RPCs.
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Pathologic examination of the sentinel lymph nodes (SLNs) in patients with breast cancer has been impacted by the publication of practicing changing trials over the last decade. With evidence from the ACOSOG Z0011 trial to suggest that there is no significant benefit to axillary lymph node dissection (ALND) in early-stage breast cancer patients with up to 2 positive SLNs, the rate of ALND, and in turn, intraoperative evaluation of SLNs has significantly decreased. It is of limited clinical significance to pursue multiple levels and cytokeratin immunohistochemistry to detect occult small metastases, such as isolated tumor cells and micrometastases, in this setting. Patients treated with neoadjuvant therapy, who represent a population with more extensive disease and aggressive tumor biology, were not included in Z0011 and similar trials, and thus, the evidence cannot be extrapolated to them. Recent trials have supported the safety and accuracy of sentinel lymph node biopsy (SLNB) in these patients when clinically node negative at the time of surgery. ALND remains the standard of care for any amount of residual disease in the SLNs and intraoperative evaluation of SLNs is still of value for real time surgical decision making. Given the potential prognostic significance of residual small metastases in treated lymph nodes, as well as the decreased false negative rate with the use of cytokeratin immunohistochemistry (IHC), it may be reasonable to maintain a low threshold for the use of cytokeratin IHC in post-neoadjuvant cases. Further recommendations for patients treated with neoadjuvant therapy await outcomes data from ongoing clinical trials. This review will provide an evidence-based discussion of best practices in SLN evaluation.
Is Axillary Assessment of Ductal Carcinoma In Situ of the Breast Necessary in All Cases?
2022, Journal of Surgical Research
Staging of the axilla in women with ductal carcinoma in situ (DCIS) is a point of controversy. We aimed to assess whether there is a group of patients in whom axillary assessment can be avoided and whether the likelihood of underdiagnosis of infiltrating carcinoma is sufficient to justify this evaluation.
This was a multicenter, prospective, observational study of patients who were operated on between 2008 and 2018 in three Spanish hospitals, with a diagnosis by radiological or excisional biopsy of DCIS and clinically and radiologically negative axilla.
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Detection and prognostic significance of isolated tumor cells and micrometastases in pelvic lymph nodes of patients with early ovarian clear cell carcinoma
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Ovarian clear cell carcinoma (OCCC) accounts for approximately 18% of all epithelial ovarian malignancies in Taiwan and portends a poor prognosis. Here, we sought to investigate whether immunohistochemistry with an anti-pan-cytokeratin antibody cocktail (AE1/AE3) can be used as an adjunct to hematoxylin and eosin (H&E) staining for improving the detection of isolated tumor cells (ITCs) and micrometastasis to pelvic lymph nodes (LNs). We also assessed whether these lesions may predict disease recurrence.
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Clusters with a positive AE1/AE3 staining were identified in five (2.53%) of the 197 patients (ITCs, n = 3; micrometastasis, n = 2). Four patients had no evidence of disease recurrence but a patient recurred at follow-up. Metastatic foci of patients with stage IIIA1 disease were all >2.0 mm in size.
Immunohistochemical staining with AE1/AE3 can identify micrometastasis or ITCs in LNs missed on routine H&E staining. The role of micrometastasis in predicting recurrent OCCC and implementing on treatment strategies requires further investigation.
Pathological process for sentinel lymph node
2020, Bulletin du Cancer
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ArticlesRole of immunohistochemical detection of lymph-node metastases in management of breast cancer

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Lancet

Hum Pathol

Eur J Cancer

Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer: an NSABP update

Cancer

Prognostic factors in breast cancer

Semin Surg Oncol

Prolonged disease free survival after one course of perioperative adjuvant chemotherapy for node negative breast cancer

N Engl J Med

Prognostic importance of occult axillary lymph node micrometastases from breast cancers

Lancet

Antigen retrieval immunohistochemistry: past, present and future

J Histochem Cytochem

Obscure axillary lymph-node metastases in carcinoma of the breast

Cancer

Detection and significance of occult metastases in node-negative breast cancer

Br J Surg

Articles
Role of immunohistochemical detection of lymph-node metastases in management of breast cancer