Detection of Micrometasteses In Lymph Nodes in Cases of Carcinoma Breast by Immunohistochemistry
Keywords:
Micrometasteses, Immunohistochemistry, Serial multiple sections, Isolated tumor cells, Cytokeratin, Epithelial membrane antigen
Abstract
Background – We evaluated archived lymph nodes of breast carcinoma for micrometastases detection by serial multiple sections (SMS) and immunohistochemistry (IHC) and found increased positive lymph nodes yield which led to change in staging in few cases, treatment and prognosis. Method – Metastatic free, early breast cancer cases of 36 patients with lymph node status pN0 or pN1 were evaluated. These were the cases had been treated with modified radicle mastectomy and axillary lymph node dissection. All the lymph node was cut at 50µm interval to get 5µm thick serial sections. These serial sections (SMS) were stained with Hematoxyline and Eosin (H&E). Out of these 2 sections were subjected to Immunohistochemistry (IHC). Monoclonal antibodies chosen for IHC were panCK (Cytokeratin) and EMA (Epithelial membrane antigen) to detect micrometasteses. Results – Total 463 lymph nodes from 36 cases of carcinoma breast were studied. New serial sections (SMS) cut from 435 lymph nodes of breast revealed 16(3.67%) additional positive lymph nodes from 12 cases. Out of 16 positive lymph nodes 4 were macrometasteses and 12 were micrometastases. Immunostaining with CK antibody revealed micrometasteses in 40 of 435 (9.19%) lymph nodes and by EMA antibody 33 of 435 (7.59%). Out of 40 micrometasteses 8 were positive for isolated tumor cells (ITC). We calculated the Z value and corresponding p value between the two methods as H&E versus SMS, H&E versus IHC and SMS versus IHC for carcinoma breasts. The tests revealed that SMS and IHC are definitely the superior methods in detection of a greater number of positive lymph nodes in cases of carcinoma breast. P value for detection of micrometasteses H&E versus SMS is <0.05 (S), H&E versus IHC <0.01(S) and SMS versus IHC (<0.02). Out of 36 cases 06 cases showed change in staging and 03 out of 06 cases were upstaged from early to advanced stage carcinoma. Conclusion – Significant number of metasteses are missed by routine processing of lymph nodes on H&E staining. SMS and IHC increase the yield of metasteses in lymph nodes. CK is superior marker than EMA.References
1. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, et al. Cancer treatment and survivorship statistics. CA Cancer J Clin. 2012;62(4):220-41.
2. Abigail S Caudle, Julie A Cupp, Henry M Kuerer. Management of Axillary Disease. Surg Oncol Clin N Am. 2014 ;23(3):473-86.
3. Yadav R, Singh S, N Marwah, K Kataria, G Aggarwal, R Sen. Immunohistochemical detection of axillary lymph node micrometastases in breast cancer patients: Increasing the accuracy of detection and decreasing labor intensive serial sectioning. Indian J Cancer 2014; 51(3):267-271
4. Maaike de B, Carolien H.M. van Deurzen, George F. Borm, Paul. van Diest, Eddy M.M. Adang et al. Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer. N Engl J Med 2009; 361:653-663
5. Indu RN, Anand JM, Vijaykumar DK. Detection of micrometastasis in axillary lymph nodes of breast carcinoma patients and its association with clinical outcome. Indian J Pathol Microbiol. 2018; 61 ( 3 ): 330-33
6. Donald L.W, David N.K, Edward A.M, Takamaru A, Brenda L. W, Seth P. H et al. Detection of Occult Sentinel Lymph Node Micrometastases by Immunohistochemistry in Breast Cancer An N S A B P Protocol B - 3 2 Quality Assurance Study. Cancer 2006;107:661–7.
7. Jeremy St. T. Retrieval, handling and assessment of lymph nodes in cancer resection specimens. Current Diagnostic Pathology 2006;12,75-82.
8. Patricia T, Kurian J. J, and Edward Y. Issues Related to Sentinel Lymph Node Assessment in the Management of Breast Cancer—What Are Relevant in Pathology Reports? Pathology Research International 2011; 7
9. Rampaul R, Miremadi A, Pinder S, et al. Pathological validation and significance of micrometastesis in sentinel nodes in primary breast cancer. Breast cancer Res 2001;3:113-116.
10. Rosen PP, Saigo P, Braum DW Jr, et al. axillary micro and macrometasteses in breast cancers; prognostic significance of tumor size. Ann Surg.1981;194(5):585-91.
11. Wells CA, Heryet A, Brochier J, Gatter KC, Mason DY. The immunohistochemical detection of micrometasteses in breast cancer. Br J Cancer 1987;55(3):392-8.
12. de Mascarel I, Bonichon F, Coindre JM, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometasteses assessed by two special techniques: reevaluation with longer follow up. Br J Cancer. 1992;66(3);523-722.
13. S E Clare, S F Sener W. Wilkens R, et al. Prognostic significance of occult lymph node metasteses in node-negative breast cancer. Ann Surg Oncol 1997;4:447-51.
14. Hainsworth PJ, Tjandra J, Stillwell RG,et al. Detection and significance of occult metasteses in node negative breast cancer. Br J Surgery 1993;80:459-63
15. Elson CE, Kulfe D, Johnson WW. Immunohistochemical detection and significance of lymph node micrometasteses in breast carcinoma. Anal Quani Cytol Histol 1993;15:171-8.
16. J. Reed, M. Rosman, K.M. Verbanac, et al. Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective. J Am Coll Surg 2009;208:333-340
17. Aysegul A. Sahin, Merih Guray, and Kelly K. Hunt. Identification and Biologic Significance of Micrometastases in Axillary Lymph Nodes in Patients With Invasive Breast Cancer. Arch Pathol Lab Med 2009;133:(6) 869-878
18. A.E. Giuliano, K.K. Hunt, K.V. Ballman, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial JAMA;2011: 569-575
19. Neville AM, Price K, Gelber RD, Goldhirsch A. Axillary node micrometastases and breast cancer. Lancet 1991;337(8749): 1110
20. Bussolatti G, Gugliotta P, Morra J, Pietribiasi F, Berardengo E. The immunohistochemical detection of lymph node metasteses from infilterating lobular carcinoma of the breast. Br J Cancer 1986; 54(4):631-6.
21. Millis RR, Springall R, Lee AHS, et al. Occult axillary lymph node metasteses are of no prognostic significance in breast cancer. Br J Cancer 2002;86:396-401
22. V. Galimberti, B.F. Cole, S. Zurrida, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases Lancet Oncol;14 (2013): 297-305
2. Abigail S Caudle, Julie A Cupp, Henry M Kuerer. Management of Axillary Disease. Surg Oncol Clin N Am. 2014 ;23(3):473-86.
3. Yadav R, Singh S, N Marwah, K Kataria, G Aggarwal, R Sen. Immunohistochemical detection of axillary lymph node micrometastases in breast cancer patients: Increasing the accuracy of detection and decreasing labor intensive serial sectioning. Indian J Cancer 2014; 51(3):267-271
4. Maaike de B, Carolien H.M. van Deurzen, George F. Borm, Paul. van Diest, Eddy M.M. Adang et al. Micrometastases or Isolated Tumor Cells and the Outcome of Breast Cancer. N Engl J Med 2009; 361:653-663
5. Indu RN, Anand JM, Vijaykumar DK. Detection of micrometastasis in axillary lymph nodes of breast carcinoma patients and its association with clinical outcome. Indian J Pathol Microbiol. 2018; 61 ( 3 ): 330-33
6. Donald L.W, David N.K, Edward A.M, Takamaru A, Brenda L. W, Seth P. H et al. Detection of Occult Sentinel Lymph Node Micrometastases by Immunohistochemistry in Breast Cancer An N S A B P Protocol B - 3 2 Quality Assurance Study. Cancer 2006;107:661–7.
7. Jeremy St. T. Retrieval, handling and assessment of lymph nodes in cancer resection specimens. Current Diagnostic Pathology 2006;12,75-82.
8. Patricia T, Kurian J. J, and Edward Y. Issues Related to Sentinel Lymph Node Assessment in the Management of Breast Cancer—What Are Relevant in Pathology Reports? Pathology Research International 2011; 7
9. Rampaul R, Miremadi A, Pinder S, et al. Pathological validation and significance of micrometastesis in sentinel nodes in primary breast cancer. Breast cancer Res 2001;3:113-116.
10. Rosen PP, Saigo P, Braum DW Jr, et al. axillary micro and macrometasteses in breast cancers; prognostic significance of tumor size. Ann Surg.1981;194(5):585-91.
11. Wells CA, Heryet A, Brochier J, Gatter KC, Mason DY. The immunohistochemical detection of micrometasteses in breast cancer. Br J Cancer 1987;55(3):392-8.
12. de Mascarel I, Bonichon F, Coindre JM, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometasteses assessed by two special techniques: reevaluation with longer follow up. Br J Cancer. 1992;66(3);523-722.
13. S E Clare, S F Sener W. Wilkens R, et al. Prognostic significance of occult lymph node metasteses in node-negative breast cancer. Ann Surg Oncol 1997;4:447-51.
14. Hainsworth PJ, Tjandra J, Stillwell RG,et al. Detection and significance of occult metasteses in node negative breast cancer. Br J Surgery 1993;80:459-63
15. Elson CE, Kulfe D, Johnson WW. Immunohistochemical detection and significance of lymph node micrometasteses in breast carcinoma. Anal Quani Cytol Histol 1993;15:171-8.
16. J. Reed, M. Rosman, K.M. Verbanac, et al. Prognostic implications of isolated tumor cells and micrometastases in sentinel nodes of patients with invasive breast cancer: 10-year analysis of patients enrolled in the prospective. J Am Coll Surg 2009;208:333-340
17. Aysegul A. Sahin, Merih Guray, and Kelly K. Hunt. Identification and Biologic Significance of Micrometastases in Axillary Lymph Nodes in Patients With Invasive Breast Cancer. Arch Pathol Lab Med 2009;133:(6) 869-878
18. A.E. Giuliano, K.K. Hunt, K.V. Ballman, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial JAMA;2011: 569-575
19. Neville AM, Price K, Gelber RD, Goldhirsch A. Axillary node micrometastases and breast cancer. Lancet 1991;337(8749): 1110
20. Bussolatti G, Gugliotta P, Morra J, Pietribiasi F, Berardengo E. The immunohistochemical detection of lymph node metasteses from infilterating lobular carcinoma of the breast. Br J Cancer 1986; 54(4):631-6.
21. Millis RR, Springall R, Lee AHS, et al. Occult axillary lymph node metasteses are of no prognostic significance in breast cancer. Br J Cancer 2002;86:396-401
22. V. Galimberti, B.F. Cole, S. Zurrida, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases Lancet Oncol;14 (2013): 297-305
Published
01-09-2020
Issue
Section
Original Article
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access at http://opcit.eprints.org/oacitation-biblio.html).
