Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease

Richard J Cote, P. P. Rosen, T. B. Hakes, M. Sedira, M. Bazinet, D. W. Kinne, L. J. Old, M. P. Osborne

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Thirty-five to 40% of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Reding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normall individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35% (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41% (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23 (three of 13) of patients with TNM stage I disease, 38% (13 of 34) of patients with stage II disease, and 50% (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size or lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.

Original languageEnglish
Pages (from-to)333-340
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume12
Issue number5
StatePublished - Jan 1 1988
Externally publishedYes

Fingerprint

Bone Marrow
Monoclonal Antibodies
Breast Neoplasms
Neoplasm Metastasis
Lymph Nodes
Antigens
Epithelial Cells
Bone Marrow Cells
Bone Marrow Neoplasms
Neoplasms
Cell Biology
Lymphoma
Leukemia
Therapeutics
Epithelium
Cell Membrane
Carcinoma

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Cote, R. J., Rosen, P. P., Hakes, T. B., Sedira, M., Bazinet, M., Kinne, D. W., ... Osborne, M. P. (1988). Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease. American Journal of Surgical Pathology, 12(5), 333-340.

Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease. / Cote, Richard J; Rosen, P. P.; Hakes, T. B.; Sedira, M.; Bazinet, M.; Kinne, D. W.; Old, L. J.; Osborne, M. P.

In: American Journal of Surgical Pathology, Vol. 12, No. 5, 01.01.1988, p. 333-340.

Research output: Contribution to journalArticle

Cote, RJ, Rosen, PP, Hakes, TB, Sedira, M, Bazinet, M, Kinne, DW, Old, LJ & Osborne, MP 1988, 'Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease', American Journal of Surgical Pathology, vol. 12, no. 5, pp. 333-340.
Cote, Richard J ; Rosen, P. P. ; Hakes, T. B. ; Sedira, M. ; Bazinet, M. ; Kinne, D. W. ; Old, L. J. ; Osborne, M. P. / Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease. In: American Journal of Surgical Pathology. 1988 ; Vol. 12, No. 5. pp. 333-340.
@article{c71cd80479ea4f3bbb78bd3990c68d8b,
title = "Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease",
abstract = "Thirty-five to 40{\%} of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Reding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normall individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35{\%} (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41{\%} (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23 (three of 13) of patients with TNM stage I disease, 38{\%} (13 of 34) of patients with stage II disease, and 50{\%} (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size or lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.",
author = "Cote, {Richard J} and Rosen, {P. P.} and Hakes, {T. B.} and M. Sedira and M. Bazinet and Kinne, {D. W.} and Old, {L. J.} and Osborne, {M. P.}",
year = "1988",
month = "1",
day = "1",
language = "English",
volume = "12",
pages = "333--340",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease

AU - Cote, Richard J

AU - Rosen, P. P.

AU - Hakes, T. B.

AU - Sedira, M.

AU - Bazinet, M.

AU - Kinne, D. W.

AU - Old, L. J.

AU - Osborne, M. P.

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Thirty-five to 40% of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Reding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normall individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35% (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41% (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23 (three of 13) of patients with TNM stage I disease, 38% (13 of 34) of patients with stage II disease, and 50% (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size or lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.

AB - Thirty-five to 40% of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Reding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normall individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35% (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41% (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23 (three of 13) of patients with TNM stage I disease, 38% (13 of 34) of patients with stage II disease, and 50% (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size or lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.

UR - http://www.scopus.com/inward/record.url?scp=0023876977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023876977&partnerID=8YFLogxK

M3 - Article

C2 - 3364618

AN - SCOPUS:0023876977

VL - 12

SP - 333

EP - 340

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 5

ER -