A human monoclonal autoantibody to breast cancer identifies the PDZ domain containing protein GIPC1 as a novel breast cancer-associated antigen

<p>Abstract</p> <p>Background</p> <p>We have been studying the native autoimmune response to cancer through the isolation of human monoclonal antibodies that are cancer specific from cancer patients. To facilitate this work we previously developed a fusion partner cell line for human lymphocytes, MFP-2, that fuses efficiently with both human lymph node lymphocytes and peripheral blood lymphocytes. Using this unique trioma fusion partner cell line we isolated a panel of autologous human monoclonal antibodies, from both peripheral blood and lymph node lymphocytes, which are representative of the native repertoire of anti-cancer specific antibodies from breast cancer patients.</p> <p>Methods</p> <p>The current study employs immunocytochemistry, immunohistochemistry, Western blot analysis as well as Northern blots, Scatchard binding studies and finally SEREX analysis for target antigen identification.</p> <p>Results</p> <p>By application of an expression cloning technique known as SEREX, we determined that the target antigen for two monoclonal antibodies, 27.B1 and 27.F7, derived from lymph node B-cells of a breast cancer patient, is the PDZ domain-containing protein known as GIPC1. This protein is highly expressed not only in cultured human breast cancer cells, but also in primary and metastatic tumor tissues and its overexpression appears to be cancer cell specific. Confocal microscopy revealed cell membrane and cytoplasmic localization of the target protein, which is consistent with previous studies of this protein.</p> <p>Conclusion</p> <p>We have determined that GIPC1 is a novel breast cancer-associated immunogenic antigen that is overexpressed in breast cancer. Its role, however, in the initiation and/or progression of breast cancer remains unclear and needs further clarification.</p

Conducting Molecular Epidemiological Research in the Age of HIPAA: A Multi-Institutional Case-Control Study of Breast Cancer in African-American and European-American Women

Breast cancer in African-American (AA) women occurs at an earlier age than in European-American (EA) women and is more likely to have aggressive features associated with poorer prognosis, such as high-grade and negative estrogen receptor (ER) status. The mechanisms underlying these differences are unknown. To address this, we conducted a case-control study to evaluate risk factors for high-grade ER- disease in both AA and EA women. With the onset of the Health Insurance Portability and Accountability Act of 1996, creative measures were needed to adapt case ascertainment and contact procedures to this new environment of patient privacy. In this paper, we report on our approach to establishing a multicenter study of breast cancer in New York and New Jersey, provide preliminary distributions of demographic and pathologic characteristics among case and control participants by race, and contrast participation rates by approaches to case ascertainment, with discussion of strengths and weaknesses

A Randomized Prospective Study of Lumpectomy Margin Assessment with Use of MarginProbe in Patients with Nonpalpable Breast Malignancies

BACKGROUND: The presence of tumor cells at the margins of breast lumpectomy specimens is associated with an increased risk of ipsilateral tumor recurrence. Twenty to 30 % of patients undergoing breast-conserving surgery require second procedures to achieve negative margins. This study evaluated the adjunctive use of the MarginProbe device (Dune Medical Devices Ltd, Caesarea, Israel) in providing real-time intraoperative assessment of lumpectomy margins. METHODS: This multicenter randomized trial enrolled patients with nonpalpable breast malignancies. The study evaluated MarginProbe use in addition to standard intraoperative methods for margin assessment. After specimen removal and inspection, patients were randomized to device or control arms. In the device arm, MarginProbe was used to examine the main lumpectomy specimens and direct additional excision of positive margins. Intraoperative imaging was used in both arms; no intraoperative pathology assessment was permitted. RESULTS: In total, 596 patients were enrolled. False-negative rates were 24.8 and 66.1 % and false-positive rates were 53.6 and 16.6 % in the device and control arms, respectively. All positive margins on positive main specimens were resected in 62 % (101 of 163) of cases in the device arm, versus 22 % (33 of 147) in the control arm (p < 0.001). A total of 19.8 % (59 of 298) of patients in the device arm underwent a reexcision procedure compared with 25.8 % (77 of 298) in the control arm (6 % absolute, 23 % relative reduction). The difference in tissue volume removed was not significant. CONCLUSIONS: Adjunctive use of the MarginProbe device during breast-conserving surgery improved surgeons’ ability to identify and resect positive lumpectomy margins in the absence of intraoperative pathology assessment, reducing the number of patients requiring reexcision. MarginProbe may aid performance of breast-conserving surgery by reducing the burden of reexcision procedures for patients and the health care system

Incidence of Occult Carcinoma and High-Risk Lesions in Mammaplasty Specimens

Objectives. To determine the incidence and type of premalignant or malignant changes in mammaplasty specimens and to determine the incidence of these changes according to age distribution. Methods. Retrospective database review of patients who underwent a reduction mammaplasty between 1999 and 2009 was performed from pathology records at a single institution. Results. 700 patients were identified. Of the 644 patients who had bilateral reductions, 25 (4%) had significant pathologic findings. The likelihood of finding premalignant changes or cancer increased with advancing patient age (0.8 percent for patients <40 years old and 10 percent for patients >60 years old). Of the 56 patients who underwent unilateral mammaplasty, 12 patients (21%) had significant pathologic findings. The incidence of finding premalignant changes or cancer in this population also increased with advancing patient age (0 for patients <40 years old to 25 percent for patients >60 years old). Conclusions. When a unilateral mammaplasty is performed to match a breast reconstructed after cancer surgery, the likelihood of identifying premalignant changes or cancer increases more than fourfold. Therefore, one should consider additional radiologic imaging in the preoperative workup of patients with a history of carcinoma prior to undergoing unilateral mammaplasty

Incidence of Occult Carcinoma and High-Risk Lesions in Mammaplasty Specimens

Objectives. To determine the incidence and type of premalignant or malignant changes in mammaplasty specimens and to determine the incidence of these changes according to age distribution. Methods. Retrospective database review of patients who underwent a reduction mammaplasty between 1999 and 2009 was performed from pathology records at a single institution. Results. 700 patients were identified. Of the 644 patients who had bilateral reductions, 25 (4%) had significant pathologic findings. The likelihood of finding premalignant changes or cancer increased with advancing patient age (0.8 percent for patients &lt;40 years old and 10 percent for patients &gt;60 years old). Of the 56 patients who underwent unilateral mammaplasty, 12 patients (21%) had significant pathologic findings. The incidence of finding premalignant changes or cancer in this population also increased with advancing patient age (0 for patients &lt;40 years old to 25 percent for patients &gt;60 years old). Conclusions. When a unilateral mammaplasty is performed to match a breast reconstructed after cancer surgery, the likelihood of identifying premalignant changes or cancer increases more than fourfold. Therefore, one should consider additional radiologic imaging in the preoperative workup of patients with a history of carcinoma prior to undergoing unilateral mammaplasty. Background There were more than 83,000 reduction mammaplasties performed in the United States in 2010 Methods A retrospective review was performed using the computerized pathology database at St. Luke&apos;s-Roosevelt Hospital Center, New York, NY, USA. The database was searched for &quot;mammaplasty&quot; between 1999 and 2009. Patients included in the study underwent either bilateral reduction mammaplasty or unilateral reduction mammaplasty to match a reconstructed breast after breast cancer surgery. Their operative reports and pathology reports were reviewed. Three random sections were taken from specimens of patients undergoing bilateral reduction and up to 8 random sections were taken from specimens of patients undergoing unilateral reduction. High risk lesions included atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS). Carcinoma included ductal carcinoma in situ (DCIS) and infiltrating ductal carcinoma (IDC). The patients were then stratified according to their age at the time of surgery. The patients over age 40 had mammography within a year of the surgery, as well as clinical breast exams before the procedure. Patients wer