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

McGuckin, Michael A.; Cummings, Margaret C.; Walsh, Miriam; Höhn, B; Bennett, Ian C.; Wright, Robert F.

doi:10.1038/bjc.1996.16

Cited by 227 publications

(148 citation statements)

References 23 publications

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“…On the other hand, lobular carcinomas and better prognosis tumor types (cribriform, medullary, mucinous, and tubular) showed a lower incidence of metastatic lymph nodes (28). Small occult metastases were detected in 13% of the cases, consistently with earlier reports (5, 6, 8 -11, 24), and were more frequent in lobular than in ductal carcinomas (Table 1), consistent with previous reports (10,13). An unbiased case distribution is also supported by corresponding estrogen receptor and Her-2/neu expression profiles in pN 0 and pN 1 cases, and by the younger age and worse average grading and pathologic T stage of pN 1 cases.…”

Section: Discussionsupporting

confidence: 82%

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Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients

Querzoli

Pedriali

Rinaldi

et al. 2006

Clinical Cancer Research

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Purpose: Early breast cancer presents with a remarkable heterogeneity of outcomes.Undetected, microscopic lymph node tumor deposits may account for a significant fraction of this prognostic diversity. Thus, we systematically evaluated the presence of lymph node tumor cell deposits V0.2 mm in diameter [pN 0(i+) , nanometastases] and analyzed their prognostic effect. Experimental Design: Single-institution, consecutive patients with 8 years of median follow-up (n = 702) were studied. To maximize chances of detecting micrometastases and nanometastases, whole-axilla dissections were analyzed. pN 0 cases (n = 377) were systematically reevaluated by lymph node (n = 6676) step-sectioning and anticytokeratin immunohistochemical analysis. The risk of first adverse events and of distant relapse of bona fide pN 0 patients was compared with that of pN 0(i+) , pN 1mi , and pN 1 cases. Results: Minimal lymph node deposits were revealed in 13% of pN 0 patients.The hazard ratio for all adverse events of pN 0(i+) versus pN 0(iÀ) was 2.51 (P = 0.00019). Hazards of pN 1mi and pN 0(i+) cases were not significantly different. A multivariate Cox model showed a hazard ratio of 2.16 for grouped pN 0(i+) /pN 1mi versus pN 0(iÀ) (P = 0.0005). Crude cumulative incidence curves for metastatic relapse were also significantly different (Gray's test m 2 = 5.54, P = 0.019). Conclusion: Nanometastases are a strong risk factor for disease-free survival and for metastatic relapse. These findings support the inclusion of procedures for nanometastasis detection in tumor-node-metastasis staging.The tumor-node-metastasis (TNM) staging system for breast cancer (1) has proven invaluable in categorizing the extent of neoplastic disease, and as a basis to estimate prognosis and to direct treatment (2). However, this has not lead to the definition of tightly homogeneous prognostic classes, as considerable heterogeneity of outcomes can be observed among disease cases currently categorized as similar. This is particularly evident in the case of small breast tumors (2). We argued that a diverse extent of lymph node dissemination at early stages of disease may account for diverse disease recurrence dynamics. The principle that the macroscopic burden of metastatic cells (e.g., number of invaded lymph nodes) dictates different risks of disease recurrence has been recognized (1,3). This principle might be equally important at the low end of the spectrum, i.e., in the case of microscopic tumor cell deposits (1, 4).Serial sectioning coupled to immunohistochemical analysis has considerably improved the detection of small tumor cell clusters in lymph nodes (5 -10). Occult metastases can indeed be identified in up to 30% of cases previously classified as pN 0 (7 -9), in 14% to 20% of the cases by single lymph node sections (9, 10). Studies based on these procedures have shown that axillary lymph node microinvasion is a prognostic factor for breast cancer patients, and is associated with poorer diseasefree and overall survival (7, 8, 11 -13). As a consequenc...

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Section: Discussionsupporting

confidence: 82%

“…A larger study by Cote et al (9) was based on immunohistochemical analysis on single lymph node sections, and this can be affected by serious sampling errors (13). Nevertheless, taken together, these analyses provided a coherent indication on an adverse prognostic effect of micrometastases (1, 7 -11, 24).…”

Section: Discussionmentioning

confidence: 99%

Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients

Querzoli

Pedriali

Rinaldi

et al. 2006

Clinical Cancer Research

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“…The most important prognostic factor is the stage of tumor at diagnosis as classified in TNM tumor staging, including the involvement of axillary regional lymph nodes and metastases of distant organs. (4,5) Until now, we have used a few immunohistochemically detectable markers relevant for the pathologic process and the prognosis of breast cancer, although it has not been satisfactory. Therefore, it is important to identify a potential tumor marker that is associated with pathophysiologic processes of breast carcinoma.…”

Section: Introductionmentioning

confidence: 99%

A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer

2007

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INTRODUCTIONBreast carcinoma is one of the most common malignancies affecting women worldwide. Recent research for tumor biology has resulted in new insights in the regulation of cell kinetics, invasion and metastasis.(1-3) But, the pathogenic mechanism underlying development and progression of breast carcinoma is still largely unknown. The most important prognostic factor is the stage of tumor at diagnosis as classified in TNM tumor staging, including the involvement of axillary regional lymph nodes and metastases of distant organs.(4, 5) Until now, we have used a few immunohistochemically detectable markers relevant for the pathologic process and the prognosis of breast cancer, although it has not been satisfactory. Therefore, it is important to identify a potential tumor marker that is associated with pathophysiologic processes of breast carcinoma. Purpose:It is important to identify a potential tumor marker that is associated with pathophysiologic processes of breast cancer. N-Myc downstream regulated genes (NDRG) are composed of four subtypes (NDRG 1-4) and NDRG2 gene has been reported as a specifically expressed gene in the human solid tumor including breast cancer. Although NDRG2 inhibits cell proliferation and promote differentiation, the molecular basis of the tumor-suppressor activity of NDRG2 in breast cancer is unknown. Herein, we tried to reveal the correlations between the expression of NDRG2 and the various clinicopathologic prognostic factors and evaluate its functional and pathophysiological roles in tumorigenesis of breast cancer. Methods: We were obtained the 67 breast cancers and paired normal tissue samples from patients who operated for breast cancer between June 2002 and June 2004. The expression of NDRG2 were measured with immunohistochemistry using monoclonal antibody and it was used eukaryotic transfection to manipulate the expression in MDA-MB-231 breast cancer cell line. Cell proliferation analysis were evaluated with trypan blue stain and status of differentially-expressed genes by NDRG2 overexpression were investigated with oligo microarray chip analysis. Results: Significant difference of NDRG2 mRNA expression between breast cancer and normal tissue was not detected. However, NDRG2 was significantly down-regulated in breast cancer tissue, compared to normal tissue (p<0.0001). It was a inverse-correlation between the NDRG2 expression and tumor size, histologic grade although other clinicopathological parameters such as axillary lymph node metastasis were not correlated. Overexpression of NDRG2 in MDA-MB-231 cell showed a decrease of cell proliferation compared with Mock control. Of the 24,000 genes, 64 genes were increased in expression while 256 genes including cyclin D1 were repressed by NDRG2 overexpression. Conclusion: Our results suggest that NDRG2 can function as a regulator of cell differentiation and cell cycle (as a tumor suppressor gene) in the early stage of breast cancer. In addition, NDRG2 protein indicates a prognostic tumor marker for breast cancer.

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“…The use of specific markers in diagnosing occult metastasis has been utilized in a number of malignancies, such as breast carcinoma, melanoma, gynecologic malignancies, oral and head and neck malignancies, colorectal cancer, and Merkel cell carcinoma. [12][13][14][15][16][17] Although originally developed in other organs, sentinel lymph node biopsy has gained widespread use in breast cancer. 18 On the basis of the results of large randomized trials confirming its efficacy and reduced morbidity, sentinel lymph node biopsy has become a standard of care for axillary evaluation in breast cancer patients with early stage disease in many institutions.…”

Section: Discussionmentioning

confidence: 99%

The role of OCT4 immunohistochemistry in evaluation of retroperitoneal lymph node dissections: a pilot study

et al. 2013

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We investigated the role of OCT4 immunohistochemical staining in detecting germ cell tumor lymph node metastases. Retroperitoneal lymph node dissection is important for staging and treatment of testicular germ cell tumors, and OCT4 is sensitive and specific for pluripotent testicular germ cell tumors; however, micrometastases, particularly from seminoma, can be difficult to detect. We examined 262 lymph nodes in 45 retroperitoneal lymph node dissection specimens from germ cell tumor patients. Specimens were categorized as postchemotherapy and untreated retroperitoneal lymph node dissection with or without clinical suspicion, based on lymphadenopathy or elevated serum germ cell tumor markers. Sections were stained with anti-OCT4 antibody. Twenty-one additional positive lymph nodes in 12 cases were detected to harbor scattered seminoma cells, singly and in small clusters, from 256 previously considered benign in: untreated retroperitoneal lymph node dissection with clinical suspicion (13% increase), postchemotherapy retroperitoneal lymph node dissection (7%), and untreated retroperitoneal lymph node dissection without suspicion (4%). However, no patient with an entirely negative dissection specimen was reclassified as positive. OCT4 immunohistochemistry detected scattered seminoma cells and small clusters of seminoma cells in lymph nodes previously considered to be benign for an overall increase of 8%, greatest in the setting of untreated retroperitoneal lymph node dissection with clinical suspicion. However, immunohistochemistry did not convert any entirely negative specimen to positive. Future studies will be useful to determine whether the small volume of disease detected by immunohistochemistry has the same impact as routinely detected lymph node metastases.

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

Cited by 227 publications

References 23 publications

Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients

Axillary Lymph Node Nanometastases Are Prognostic Factors for Disease-Free Survival and Metastatic Relapse in Breast Cancer Patients

A Study for Expression and Biological Function of N-myc Downstream Regulated Gene 2 in Breast Cancer

The role of OCT4 immunohistochemistry in evaluation of retroperitoneal lymph node dissections: a pilot study

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