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Screening endometrial cancer for Lynch syndrome in a Brazilian public health care system cancer center
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Abstracts / Gynecologic Oncology 130 (2013) e1–e169
but before chemotherapy, 22% during chemotherapy, and 28% after chemotherapy. Similarly, women’s opinions varied as to the best time for GC, including before surgery (11%), after surgery but before chemotherapy (18%), during chemotherapy (24%), and after chemotherapy (40%). More than half the women said they were comfortable receiving the GT results by phone, but one third of responders considered an office visit to be the preferred setting to disclose GT results. Conclusions: Patients views regarding the best time to be referred for and to undergo GC vary greatly. Due to the high mortality of this disease, clinicians should discuss referral for GC early and personalize the timing of the referral to their patients’ desires. While many patients are comfortable receiving their results over the phone, the subset of patients who prefer an office visit should be identified at the time of their initial GC. doi:10.1016/j.ygyno.2013.04.293
235 Evaluation of immune function in patients with hereditary cancers L. Parker1, H. Strickland2, D. Clark1, D. Metzinger1, M. Milam1, D. Taylor1, C. Gercel-Taylor1. 1University of Louisville, Louisville, KY, 2Naval Medical Center San Diego, San Diego, CA. Objective: Patients with hereditary cancers have been shown to have relatively better outcomes than those with sporadic cancers. Strong lymphocytic infiltration has been reported as a characteristic of colon cancers in patients with Lynch syndrome or sporadic tumors with high microsatellite instability. The purpose of this study was to evaluate gene expression profiles for genes involved in T- and B-cell activation in patients with hereditary cancer syndromes. Methods: Ten patients with a diagnosis of Lynch syndrome, BRCA1 mutation, BRCA2 mutation, or juvenile polyposis syndrome confirmed by genetic testing or by immunohistochemical staining of tumor were enrolled in the institutional review board-approved trial. Blood (10 mL) was drawn into heparinized tubes from study participants. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation on Ficoll-Hypaque. RNA was isolated from the PBMC’s by the Trizol method. T- and B-cell activation was studied by polymerase chain reaction array containing 84 relevant genes. Results: Thirty-four genes were expressed significantly less than the controls in all of the 10 patients tested. Most affected genes were CCR3, CD40, CD5, CD8A, CXCR3, IL12RB1, TLR9, and TNFSF14. These genes are all involved in pathways related to T-cell activation. In addition, CSF-2 and IL12B were not expressed or expressed in very low levels in all of the patients. CSF-2 is involved in T-cell polarization while IL12B plays a role in Th1, Th2 differentiation. A subgroup of BRCA1 patients were characterized by the lack of expression of CD28, CD80, CD40, HDAC5, and KIF13B. Conclusions: A pilot study of patients with hereditary cancers demonstrates that pathways related to T-cell activation may play a central role in the susceptibility and manifestation of malignancies associated with this group. doi:10.1016/j.ygyno.2013.04.294
236 Screening endometrial cancer for Lynch syndrome in a Brazilian public health care system cancer center C. Andrade, M. Mengatto, M. Vieira, M. Cadamuro, E. Palmero, J. Oliveira, P. Bogiss, D. Viana, A. Tsunoda. Barretos Cancer Hospital, Barretos, Brazil.
Objective: Lynch syndrome (LS) is a hereditary cancer syndrome that increases the risk for colorectal and endometrial cancer (EC). To our best knowledge, our department is the first in Brazil with an organized screening program to select EC patients for genetic counseling in the context of the public health care system. Methods: Our gynecologic oncology department started to screen patients systematically for genetic counseling in April 2011. Data were prospectively collected from all patients referred due EC during their first consultation. A 6-item questionnaire was employed (histology of dilatation and curettage, age, other primary cancer, family history of LS-related cancer, and relatives with history of cancer before 50 years of age or with confirmed LS). Patients younger than 60 years or with at least 1 relative with LS-related cancer were contacted after completing their primary treatment to schedule an appointment at the oncogenetic department. After genetic counseling, patients younger than 60 years, those who had 1 first-degree relative with LS-related cancer, or those who had at least 2 seconddegree relatives with LS-related cancer and 1 who had cancer before 50 years of age were asked to test for LS using immunohistochemistry for expression of MLH1, MSH2, MSH6, and PMS2 and a blood test for microsatellite instability (MSI). Results: From April 2011 to February 2012, 50 patients were referred due EC. Thirty-five with endometrioid histology and 2 patients with undifferentiated tumors were screened using the 6-item questionnaire. Two (5.4%) screened patients had another primary cancer (1 colorectal and 1 pancreatic). Seventeen (45.9%) patients had firstdegree relatives with LS-related cancer, and 12 (32.4%) had at least 2 second-degree relatives with LS-related cancer. Only 1 patient had a relative with cancer before age 50 years. None had a relative with confirmed LS. Median age of the screened patients was 60 years (range, 31- 82 years), with 18 patients younger than 60 years. Thirty-one were screened for genetic counseling, but 3 died before the screening, 4 did not accept the invitation, and 3 did not attend the appointment. Among 11 tested women, 4 had LS with 2 having mutations in MSH2 and 2 in MSH6 genes. Among the total of cases of endometrioid EC, 10.8% had LS. Conclusions: The application of wide criteria to screen women with EC resulted in selection of fewer than one third for genetic testing. Because 10.8% of patients received the diagnosis of LS, we can assume that the detection rate for LS was adequate in this sample. doi:10.1016/j.ygyno.2013.04.295
237 Endometrial cancer screening in Lynch syndrome: Do patients report symptoms prior to diagnosis? K. Ring, S. Boyd-Rogers, Y. Amin, M. Daniels, B. Batte, K. Schmeler, E. Keeler, K. Lu. The University of Texas, MD Anderson Cancer Center, Houston, TX. Objective: With increasing awareness and testing for Lynch syndrome in patients with colorectal and endometrial cancer, an increasing number of individuals have been identified who carry germline mismatch repair (MMR) gene mutations. Current guidelines for endometrial cancer screening include annual endometrial sampling. The study objectives were to evaluate patient compliance with current screening guidelines and to evaluate symptoms before diagnosis of endometrial cancer in patients undergoing screening. Methods: Clinicopathologic data for patients enrolled in a Lynch registry from 2007 through 2011 at a single institution were reviewed retrospectively. Data were collected from medical records as well as yearly surveys sent to patients enrolled in the registry. Results: Of 203 patients enrolled, 113 patients with no previous diagnosis of endometrial cancer had clinicopathologic data available for
Abstracts / Gynecologic Oncology 130 (2013) e1–e169
but before chemotherapy, 22% during chemotherapy, and 28% after chemotherapy. Similarly, women’s opinions varied as to the best time for GC, including before surgery (11%), after surgery but before chemotherapy (18%), during chemotherapy (24%), and after chemotherapy (40%). More than half the women said they were comfortable receiving the GT results by phone, but one third of responders considered an office visit to be the preferred setting to disclose GT results. Conclusions: Patients views regarding the best time to be referred for and to undergo GC vary greatly. Due to the high mortality of this disease, clinicians should discuss referral for GC early and personalize the timing of the referral to their patients’ desires. While many patients are comfortable receiving their results over the phone, the subset of patients who prefer an office visit should be identified at the time of their initial GC. doi:10.1016/j.ygyno.2013.04.293
235 Evaluation of immune function in patients with hereditary cancers L. Parker1, H. Strickland2, D. Clark1, D. Metzinger1, M. Milam1, D. Taylor1, C. Gercel-Taylor1. 1University of Louisville, Louisville, KY, 2Naval Medical Center San Diego, San Diego, CA. Objective: Patients with hereditary cancers have been shown to have relatively better outcomes than those with sporadic cancers. Strong lymphocytic infiltration has been reported as a characteristic of colon cancers in patients with Lynch syndrome or sporadic tumors with high microsatellite instability. The purpose of this study was to evaluate gene expression profiles for genes involved in T- and B-cell activation in patients with hereditary cancer syndromes. Methods: Ten patients with a diagnosis of Lynch syndrome, BRCA1 mutation, BRCA2 mutation, or juvenile polyposis syndrome confirmed by genetic testing or by immunohistochemical staining of tumor were enrolled in the institutional review board-approved trial. Blood (10 mL) was drawn into heparinized tubes from study participants. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation on Ficoll-Hypaque. RNA was isolated from the PBMC’s by the Trizol method. T- and B-cell activation was studied by polymerase chain reaction array containing 84 relevant genes. Results: Thirty-four genes were expressed significantly less than the controls in all of the 10 patients tested. Most affected genes were CCR3, CD40, CD5, CD8A, CXCR3, IL12RB1, TLR9, and TNFSF14. These genes are all involved in pathways related to T-cell activation. In addition, CSF-2 and IL12B were not expressed or expressed in very low levels in all of the patients. CSF-2 is involved in T-cell polarization while IL12B plays a role in Th1, Th2 differentiation. A subgroup of BRCA1 patients were characterized by the lack of expression of CD28, CD80, CD40, HDAC5, and KIF13B. Conclusions: A pilot study of patients with hereditary cancers demonstrates that pathways related to T-cell activation may play a central role in the susceptibility and manifestation of malignancies associated with this group. doi:10.1016/j.ygyno.2013.04.294
236 Screening endometrial cancer for Lynch syndrome in a Brazilian public health care system cancer center C. Andrade, M. Mengatto, M. Vieira, M. Cadamuro, E. Palmero, J. Oliveira, P. Bogiss, D. Viana, A. Tsunoda. Barretos Cancer Hospital, Barretos, Brazil.
Objective: Lynch syndrome (LS) is a hereditary cancer syndrome that increases the risk for colorectal and endometrial cancer (EC). To our best knowledge, our department is the first in Brazil with an organized screening program to select EC patients for genetic counseling in the context of the public health care system. Methods: Our gynecologic oncology department started to screen patients systematically for genetic counseling in April 2011. Data were prospectively collected from all patients referred due EC during their first consultation. A 6-item questionnaire was employed (histology of dilatation and curettage, age, other primary cancer, family history of LS-related cancer, and relatives with history of cancer before 50 years of age or with confirmed LS). Patients younger than 60 years or with at least 1 relative with LS-related cancer were contacted after completing their primary treatment to schedule an appointment at the oncogenetic department. After genetic counseling, patients younger than 60 years, those who had 1 first-degree relative with LS-related cancer, or those who had at least 2 seconddegree relatives with LS-related cancer and 1 who had cancer before 50 years of age were asked to test for LS using immunohistochemistry for expression of MLH1, MSH2, MSH6, and PMS2 and a blood test for microsatellite instability (MSI). Results: From April 2011 to February 2012, 50 patients were referred due EC. Thirty-five with endometrioid histology and 2 patients with undifferentiated tumors were screened using the 6-item questionnaire. Two (5.4%) screened patients had another primary cancer (1 colorectal and 1 pancreatic). Seventeen (45.9%) patients had firstdegree relatives with LS-related cancer, and 12 (32.4%) had at least 2 second-degree relatives with LS-related cancer. Only 1 patient had a relative with cancer before age 50 years. None had a relative with confirmed LS. Median age of the screened patients was 60 years (range, 31- 82 years), with 18 patients younger than 60 years. Thirty-one were screened for genetic counseling, but 3 died before the screening, 4 did not accept the invitation, and 3 did not attend the appointment. Among 11 tested women, 4 had LS with 2 having mutations in MSH2 and 2 in MSH6 genes. Among the total of cases of endometrioid EC, 10.8% had LS. Conclusions: The application of wide criteria to screen women with EC resulted in selection of fewer than one third for genetic testing. Because 10.8% of patients received the diagnosis of LS, we can assume that the detection rate for LS was adequate in this sample. doi:10.1016/j.ygyno.2013.04.295
237 Endometrial cancer screening in Lynch syndrome: Do patients report symptoms prior to diagnosis? K. Ring, S. Boyd-Rogers, Y. Amin, M. Daniels, B. Batte, K. Schmeler, E. Keeler, K. Lu. The University of Texas, MD Anderson Cancer Center, Houston, TX. Objective: With increasing awareness and testing for Lynch syndrome in patients with colorectal and endometrial cancer, an increasing number of individuals have been identified who carry germline mismatch repair (MMR) gene mutations. Current guidelines for endometrial cancer screening include annual endometrial sampling. The study objectives were to evaluate patient compliance with current screening guidelines and to evaluate symptoms before diagnosis of endometrial cancer in patients undergoing screening. Methods: Clinicopathologic data for patients enrolled in a Lynch registry from 2007 through 2011 at a single institution were reviewed retrospectively. Data were collected from medical records as well as yearly surveys sent to patients enrolled in the registry. Results: Of 203 patients enrolled, 113 patients with no previous diagnosis of endometrial cancer had clinicopathologic data available for