Clinical Relevance of Reverse Transcriptase-Polymerase Chain Reaction for the Detection of Axillary Lymph Node Metastases in Breast Cancer Masahiro Sakaguchi, MD, Arvind Virmani, PhD, Marla W. Dudak, MD, George N. Peters, MD, A. Marilyn Leitch, MD, Hossein Saboorian, MD, Adi F. Gazdar, MD, and David M. Euhus, MD Background: The mammary sentinel lymph node procedure can increase the detection of axillary metastases by 45% compared with standard axillary dissection. Some investigators have reported that reverse transcriptase-polymerase chain reaction (RT-PCR) increases metastasis detection even more, but it is uncertain whether a positive RT-PCR test in the face of a negative histological evaluation is clinically meaningful. Methods: RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 was performed on sentinel and pooled nonsentinel axillary lymph nodes from 108 women with clinical stage I or II breast cancer who were followed up for a median of 40 months. Results: Axillary metastases were detected on standard tissue sections in 26% and by RT-PCR in 30%. Results for the two tests were concordant for 80% of the cases. RT-PCR upstaged 16%. Tumors from women whose lymph nodes were positive only by RT-PCR were phenotypically similar to those from women with no metastases detected by any method. Moreover, 4-year actuarial distant disease-free survival was 100% for women with metastases detected by RT-PCR only, as compared with 74% for those with metastases detected by routine histology (P = .03) and 93% for those with no metastases detected by either method (P = .04). Conclusions: Analysis of sentinel lymph nodes by RT-PCR for epithelial glycoprotein 2 and cytokeratin 19 is unlikely to provide clinically useful information. Key Words: Breast cancer—Sentinel nodes—RT-PCR—Cytokeratin-19 —EGP-2—Survival. The most important prognostic factor for patients with breast cancer is the presence of axillary lymph node metastases. However, 23% of stage I (T1N0M0) breast cancer patients who are treated with mastectomy will eventually die of the disease. 1 Better identification of micrometastatic disease in axillary lymph nodes may allow for more accurate assessment of prognosis in women with breast cancer. Special techniques, such as serial sectioning and im- munohistochemical (IHC) staining, improve the detec- tion of axillary micrometastases. Serial sectioning alone can upstage 7% to 33% of axillae, 2–4 and single-section IHC upstages 20%. 2 The sentinel lymph node proce- dure itself has improved the detection of micrometas- tases by allowing pathologists to focus on only one or two lymph nodes. In one series, application of the sentinel lymph node procedure to clinical stage I and II breast cancer patients increased the metastasis de- tection rate from 29% to 42%, largely by enhanced detection of micrometastases. 5 As methods for detecting micrometastatic disease be- come more sensitive, it is appropriate to question whether clinically meaningful information is obtained by Received January 17, 2002; accepted September 24, 2002. From the Departments of Surgery (MWD, GNP, AML, DME) and Pathology (MS, AV, HS, AFG), University of Texas Southwestern Medical Center, Dallas, Texas. Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001. Address correspondence and reprint requests to: David M. Euhus, MD, Division of Surgical Oncology, E6.222, UT Southwestern Med- ical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9155; Fax: 214-648-7965; E-mail: david.euhus@utsouthwestern.edu. Published by Lippincott Williams & Wilkins © 2003 The Society of Surgical Oncology, Inc. Annals of Surgical Oncology, 10(2):117–125 DOI: 10.1245/ASO.2003.01.010 117