The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer

doi:10.1016/S0002-9610(01)00722-X

The American Journal of Surgery

Volume 182, Issue 4, October 2001, Pages 330-334

Presented at the Second Annual Meeting of the American Society of Breast Surgeons, La Jolla, California, May 3–6, 2001.

https://doi.org/10.1016/S0002-9610(01)00722-X Get rights and content

Abstract

Background: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases.

Methods: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining.

Results: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were “upstaged” by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen.

Conclusions: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.

Section snippets

Methods

The University of Louisville Breast Cancer Sentinel Lymph Node Study is a prospective, multi-institutional study involving 226 surgeons. Participating surgeons reported consecutive cases of SLN biopsy, followed by completion level I/II axillary dissection in every patient. Informed consent was obtained in accordance with the institutional review board regulations at each institution. Patients with biopsy-proven, clinical stage T1-2, N0 breast cancer were eligible for enrollment. Some patients

Results

Between August 1997 and August 2000, a total of 1,981 patients were enrolled into the study. IHC examination of SLN was performed in sentinel node specimens from 973 patients (49%). Clinicopathologic characteristics of patients undergoing SLN biopsy are shown in Table 1. Patients who had IHC staining of their sentinel nodes were well-matched to those patients who had H&E staining alone in terms of age, tumor size, histologic subtype, tumor location, type of biopsy, type of surgery performed,

Comments

The single most important prognostic factor predicting breast cancer survival is the pathologic status of the regional lymph nodes. Accuracy of nodal evaluation is critical. Failure to detect microscopic disease in the axilla may be the source of locoregional recurrence, distant disease, and decreased survival. Conversely, use of ultra-staging techniques has potential for overstaging and subsequent misuse of adjuvant therapies. Furthermore, the prognostic significance of such occult nodal

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Citation Excerpt :
In a retrospective analysis of patients with BC who had negative SLN on standard haematoxylin and eosin staining; further analysis performed with serial sectioning and cytokeratin IHC showed 18% of patients had MM in SLN. However, such MM showed no effect on clinical outcome [101,102]. Prospective studies have also evaluated the significance of SLN MM.
The advent of sentinel lymph node biopsy (SLNB) and advances in histopathological and molecular analysis techniques have been associated with an increase in micrometastasis (MM) detection rate. However, the clinical significance of sentinel lymph node micrometastasis (SLN MM) continues to be a subject of much debate. In this article we review the literature concerning SLN MM, with particular emphasis on the prognostic significance of SLN MM. The controversies regarding histopathological assessment, clinical relevance and management implications are also discussed.
Literature review facilitated by Medline and PubMed databases. Cross referencing of the obtained articles was used to identify other relevant studies.
Published studies have reported divergent and rather conflicting results regarding the clinical significance and implications of axillary lymph node (ALN) MM in general and SLN MM in particular. Some earlier studies demonstrated no associations, however most recent studies have found SLN MM to be an indicator of poorer prognosis and to be associated with non-SLN involvement.
The use of adjuvant chemotherapy and/or hormonal manipulation therapy is associated with an improved survival in patients with SLN MM. Complete ALND may be safely omitted provided that adjuvant systemic therapy recommendations are equal to patients with node-positive disease. However, optimal management of SLN MM is yet to conclude.
Furthermore, the identification of MM remains largely dependant on the analytical technique employed and the use of immunohistochemistry (IHC) increases the detection rate of SLN MM. Discrepancies in the histopathological interpretation of TNM classification of SLN tumour burden do exist. Published studies were non-randomized and have significant limitations including a small sample size, limited follow-up period, and lack of standardization and reproducibility of pathological examination of the SLN.
Patients with SLN MM have a poorer prognosis than those who are SLN negative. Therapeutic recommendations regarding patients with SLN MM should be taken in the context of multidisciplinary team setting and in selected cases of SLN MM, complete ALND may be safely omitted. A better reproducibility of pathological interpretation of the TNM classification is required so that future therapeutic guidelines can be applied without confusion.
Clinical significance of minimal sentinel node involvement and management options
2010, Surgical Oncology Clinics of North America
Intraoperative immunohistochemistry staining of sentinel nodes in breast cancer: Clinical and economical implications
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Citation Excerpt :
In other studies, IHC was used only when the findings of the H&E frozen section were negative.9,17 This may explain the relatively high benefit intraoperative IHC staining gave in the present study compared to others.10–12,17 It could also partly explain why the procedure does not seem to significantly prolong the pathologic, and consequently, also the surgical procedures.
The study aimed to evaluate intraoperative immunohistochemistry (IHC) staining of sentinel nodes in primary breast cancer surgery. We analysed retrospectively 1209 consecutive sentinel node procedures and compared the rate of late positive metastases in sentinel node biopsy (SNB) and the duration of the surgical procedures before (n = 706) and after (n = 503) introducing intraoperative IHC on frozen section. We also did a cost analysis.
Intraoperative IHC staining led to a lowering of the late positive SNB rate. Introducing IHC gave a decrease in the late positive rate from 93 to 52% (p < 0.0001) for isolated tumour cell metastasis, from 56 to 36.4% (p < 0.02) for micrometastasis, and from 16 to 5% (p < 0.01) for macrometastasis. The surgical procedures were slightly prolonged for lumpectomies but not for mastectomies after introducing intraoperative IHC staining. The cost analysis showed an overall cost saving of approximately 40%.
In conclusion, intraoperative IHC staining of the SNB lowered the late positive rate and gave an overall cost saving.
Immunocytological Detection of Lymph Node Metastases in Dogs with Malignant Epithelial Tumours
2007, Journal of Comparative Pathology
The aim of this study was to compare immunolabelling of cytological specimens with conventional staining in the detection of metastases in lymph nodes from dogs with carcinoma. Cytological touch imprints of 161 lymph nodes from 72 dogs, as well as 50 fine needle aspirates from 23 dogs, with malignant epithelial tumours were included in the study. Immunolabelling was performed with commercially available human antibodies. Touch imprints of all lymph nodes were labelled with broad spectrum anticytokeratins AE1/AE3 and KL1. In addition, lymph node touch imprints from dogs with primary tumours that reacted positively with the specific anticytokeratins CK7 (n=104) and CK20 (n=20) were also labelled with CK7 and CK20. Fine needle aspirates of 50 lymph nodes were examined by immunolabelling with AE1/AE3. “Reference investigations” with a combination of histological and immunohistochemical methods were performed on all lymph nodes. The immunocytological detection of lymph node metastases with the broad spectrum anti-cytokeratin AE1/AE3 in imprint smears resulted in a significant increase in sensitivity (0.99 vs 0.88 [conventional stain]) and in negative predictive value (0.99 vs 0.85) (P<0.01; t-test). Micrometastases in particular were detected more readily. Specificity (0.93 vs 0.88) and positive predictive value (0.95 vs 0.90) did not differ significantly between the two techniques. Immunolabelling with KL1 was associated with lower sensitivity and negative predictive value, indicating lack of cross-reactivity of this antibody with canine epithelial cells. In fine needle aspirates the detection of lymph node metastases, especially micrometastases, was more efficient by mean of immunolabelling with AE1/AE3 than by conventional staining. The study indicated the value of immunocytological labelling for the detection of metastases in cytological specimens of canine lymph node preparations.
Accuracy of pathologic examination in detection of complete response after chemoradiation for esophageal cancer
2007, American Journal of Surgery
Although a substantial proportion of patients undergoing neoadjuvant chemoradiation for invasive esophageal cancer develop a pathologic complete response (pCR), these patients nonetheless have a poor 5-year survival rate. We hypothesized that routine pathologic examination fails to identify some residual cancer.
Patients undergoing esophagectomy for cancer at 2 tertiary care centers were identified. Archived tumor blocks were retrieved for patients with pCR, sectioned at 50-μm intervals and reexamined for residual cancer.
Seventy patients underwent neoadjuvant chemoradiation. Tumor blocks were available for 23 of 26 complete responders. A total of 159 blocks were reexamined. One patient was found to have a possible focus of residual invasive adenocarcinoma versus high-grade dysplasia. The remaining 22 patients had no residual disease.
A more aggressive examination protocol for postchemoradiation esophagectomy specimens may not result in significant upstaging. Inadequate pathologic examination is likely not a major factor in the suboptimal survival in patients with pCR.

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The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer

Abstract

Section snippets

Methods

Results

Comments

Surgery

Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases

Cancer

Lymph node micrometastases from breast carcinomareviewing the dilemma

Cancer

Minimal solid tumor involvement of regional and distant sites. When is a metastasis not a metastasis?

Cancer

Benign transport of breast epithelium into axillary lymph nodes after biopsy

Am J Clin Pathol

Safety of sentinel lymph node dissection and significance of cytokeratin micrometastases

J Clin Oncol

Relation of number of positive axillary nodes to the prognosis of patients with primary breast canceran NSABP update

Cancer

Microstaging of breast cancer patients using cytokeratin staining of the sentinel lymph node

Ann Surg Oncol