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Lynch Syndrome: Should Endometrial Cancer Patients in the 50-60 Age Group be Screened?
Abstracts
computed tomography (CT) scans were retrospectively analyzed for tissue cross-sectional area (cm2) using Slice-O-Matic software V4.3 (Tomovision, Montreal, Quebec, CA). In addition, pre- and post-NACT albumin was measured. For each patient, two stage- and age- matched controls who underwent a primary surgical approach at our institution during the same time period were randomly selected. The paired t-test and Wilcoxon signed rank test were used to compare changes in albumin and nutritional markers. Morbidity and mortality were compared using the chi-square and logrank test, respectively. Results: 38 NACT cases met inclusion criteria. Among cases, the mean age was 63.7 y, 69% had stage IIIC disease, and 100% received carboplatin and paclitaxel as primary therapy. Mean serum albumin increased significantly after NACT from 3.42 g/dL to 3.89 g/dL (p= 0.027). In addition, pre- and post-NACT assessment revealed improvement in CT scan body composition measurements (pb 0.001). Upon sub-analysis of the medically unfit cases (n= 13) and controls (n= 27), we found significantly less 30-day post-treatment morbidity in the cases who received NACT (p= 0.016, 15.4% vs. 55.6%), as well as no difference in overall survival (p= 0.96) when compared to surgical controls. Conclusion: Among women with AOC, those with poor nutritional and performance status constitute a small group at high risk for treatment-related complications. We observed objective serum and radiographic evidence of improved nutrition after NACT for AOC. More importantly, in medically unfit patients, these developments were associated with improved treatment-related morbidity, while offering similar overall survival. doi:10.1016/j.ygyno.2012.01.026
11 Lynch Syndrome: Should Endometrial Cancer Patients in the 50-60 Age Group be Screened? P. Sareen1, R. Blandon2, S. Miller3, W. Ford2, B. Shoup2. 1University of Missouri, Kansas City, MO, 2Saint Luke's Hospital, Kansas City, MO, 3Ellis Fischel Cancer Center, Columbia, MO. Objectives: Lynch syndrome increases susceptibility to multiple malignancies, most importantly colorectal cancer (CRC) and endometrial cancer (EC). Current SGO guidelines indicate a 5-10% risk of Lynch syndrome in patients younger than 50 years that have been diagnosed with EC. We hypothesize that a significant number of patients diagnosed with EC between the ages of 50-60 years may also be at risk for Lynch syndrome. Our objective is to determine the incidence of Lynch syndrome in a selected cohort of patients diagnosed with EC prior to the age of 60 years and to compare the b50 age group to the 50-60 age group. Methods: All patients diagnosed with EC before the age of 60 years from December 1, 2009 to September 30, 2011 at a single institution were identified. The institutional policy is to screen all EC patients b60 for Lynch syndrome with immunohistochemistry (IHC) molecular testing. A retrospective chart review was performed on the selected cohort. Only the tumors that underwent IHC prescreening for the four mismatch repair genes (MSH1, MSH2, MSH6 and PMS2) were included in data collection. Other variables included in subgroup analysis were personal and family history of malignancy, BMI, and EC stage, grade and histology. Results: Of 69 patients that met criteria for reflex testing, 53 had IHC staining performed on their tumor specimens. Eight patients were b50 years and 45 patients were 50-60 years. Among the patients b50 years, 1 (12.5%) had abnormal IHC testing and further gene sequencing revealed a mutation in the MSH6 gene. Among the patients ≥50 years old, 9 (20%) had abnormal IHC testing. Of these, loss of MLH1 was noted in 8/9 (89%) tumors and loss of MSH2/MSH6 was noted in 1/9 (11%). Two patients had normal gene MLH1 gene sequencing, 2 patients
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declined further testing, and 2 patients were lost to follow-up. The 3 remaining patients have had genetic testing, but the results are pending at this time. Results will be available at the time of presentation. Conclusion: A high proportion of EC patients from ages 50 to 60 years had abnormal IHC testing (20%). The majority of their tumors had a loss of MLH1 expression which can either be due to a gene mutation or hypermethylation of the MLH1 gene promoter. Also, of these patients, only 1 patient had a personal history of cancer and only 2 patients had a family history of Lynch-associated malignancies. IHC screening of EC patients less than 60 years may be reasonable in those patients with a significant family or personal history of cancer.
doi:10.1016/j.ygyno.2012.01.027
12 Nanometastases of Endometrial Carcinoma to Sentinel Lymph Nodes: The Contribution of Pathologic Ultrastaging C. Kim, F. Khoury-Collado, J. Barlin, K. Park, D. Cassella, Y. Sonoda, M. Hensley, D. Chi, R. Barakat, N. Abu-Rustum. Memorial Sloan-Kettering Cancer Center, New York, NY. Objectives: To describe the incidence of nanometastases in sentinel lymph nodes (SLN) identified at surgical staging for endometrial carcinoma (EC) and to correlate it with depth of myoinvasion (DMI) and tumor grade. Methods: We reviewed all patients (pts) who underwent primary surgery for EC with successful mapping of at least one SLN at our institution from 9/2005-4/2011. The pathology protocol for SLN ultrastaging evaluation involved cutting an additional 2 adjacent 5um sections at each of two levels, 50-um apart, from each paraffin block lacking metastatic carcinoma appreciable in a routine section stained with hematoxylin and eosin (H&E). At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anti-cytokeratin AE1:AE3. Micrometastasis (MM) was defined as a focus of metastatic cancer N0.2 mm to 2 mm. Isolated tumor cells (ITC) were defined as metastasis measuring b0.2 mm. Cytokeratin positive cells (CKPC) included the presence of single cytokeratin positive cells, the clinical significance of which is uncertain. We defined nanometastases as all cases of MM and ITC detected by pathologic ultrastaging. Results: We identified 401 pts with the following histologies: 319 (79.6%) endometrioid, 58 (14.4%) serous or clear cell, 16 (5.5%) carcinosarcoma, and 2 (0.5%) undifferentiated. There were 203 (50.5%) pts with no myometrial invasion, 145 (36.2%) with b50%, and 53 (13.2%) with ≥50%. SLN was positive for metastatic disease on initial routine H&E in 27/ 401 (6.7%). Ultrastaging detected an additional 9 (2.2%) pts with nanometastases in their SLN that would have been missed otherwise including: 2 MM, 7 ITCu (only found on ultrastaging). In 4 pts, pathologists used a combination of ultrastaging and H&E to confirm metastatic isolated tumor cells in SLN (ITCc). The total incidence of nanometastases was 13/401 (3.2%). There were 10 (2.5%) CKPC pts. The incidence of nanometastases were 1.9%, 2.2%, and 3.1% in grade 1, 2, and 3 tumors, respectively. There was an additional 4.8% incidence of nanometasasis in tumors with ≤50% myoinvasion. Conclusion: SLN mapping with pathologic ultrastaging in endometrial cancer provides an opportunity to detect nanometastases, which would otherwise be undetected with routine pathologic evaluation. The significance of this finding in pts is not yet known. These data support the incorporation of pathologic ultrastaging and SLN mapping algorithm in endometrial cancer surgery especially for the presumed low-risk group (≤50% myoinvasion). doi:10.1016/j.ygyno.2012.01.028
computed tomography (CT) scans were retrospectively analyzed for tissue cross-sectional area (cm2) using Slice-O-Matic software V4.3 (Tomovision, Montreal, Quebec, CA). In addition, pre- and post-NACT albumin was measured. For each patient, two stage- and age- matched controls who underwent a primary surgical approach at our institution during the same time period were randomly selected. The paired t-test and Wilcoxon signed rank test were used to compare changes in albumin and nutritional markers. Morbidity and mortality were compared using the chi-square and logrank test, respectively. Results: 38 NACT cases met inclusion criteria. Among cases, the mean age was 63.7 y, 69% had stage IIIC disease, and 100% received carboplatin and paclitaxel as primary therapy. Mean serum albumin increased significantly after NACT from 3.42 g/dL to 3.89 g/dL (p= 0.027). In addition, pre- and post-NACT assessment revealed improvement in CT scan body composition measurements (pb 0.001). Upon sub-analysis of the medically unfit cases (n= 13) and controls (n= 27), we found significantly less 30-day post-treatment morbidity in the cases who received NACT (p= 0.016, 15.4% vs. 55.6%), as well as no difference in overall survival (p= 0.96) when compared to surgical controls. Conclusion: Among women with AOC, those with poor nutritional and performance status constitute a small group at high risk for treatment-related complications. We observed objective serum and radiographic evidence of improved nutrition after NACT for AOC. More importantly, in medically unfit patients, these developments were associated with improved treatment-related morbidity, while offering similar overall survival. doi:10.1016/j.ygyno.2012.01.026
11 Lynch Syndrome: Should Endometrial Cancer Patients in the 50-60 Age Group be Screened? P. Sareen1, R. Blandon2, S. Miller3, W. Ford2, B. Shoup2. 1University of Missouri, Kansas City, MO, 2Saint Luke's Hospital, Kansas City, MO, 3Ellis Fischel Cancer Center, Columbia, MO. Objectives: Lynch syndrome increases susceptibility to multiple malignancies, most importantly colorectal cancer (CRC) and endometrial cancer (EC). Current SGO guidelines indicate a 5-10% risk of Lynch syndrome in patients younger than 50 years that have been diagnosed with EC. We hypothesize that a significant number of patients diagnosed with EC between the ages of 50-60 years may also be at risk for Lynch syndrome. Our objective is to determine the incidence of Lynch syndrome in a selected cohort of patients diagnosed with EC prior to the age of 60 years and to compare the b50 age group to the 50-60 age group. Methods: All patients diagnosed with EC before the age of 60 years from December 1, 2009 to September 30, 2011 at a single institution were identified. The institutional policy is to screen all EC patients b60 for Lynch syndrome with immunohistochemistry (IHC) molecular testing. A retrospective chart review was performed on the selected cohort. Only the tumors that underwent IHC prescreening for the four mismatch repair genes (MSH1, MSH2, MSH6 and PMS2) were included in data collection. Other variables included in subgroup analysis were personal and family history of malignancy, BMI, and EC stage, grade and histology. Results: Of 69 patients that met criteria for reflex testing, 53 had IHC staining performed on their tumor specimens. Eight patients were b50 years and 45 patients were 50-60 years. Among the patients b50 years, 1 (12.5%) had abnormal IHC testing and further gene sequencing revealed a mutation in the MSH6 gene. Among the patients ≥50 years old, 9 (20%) had abnormal IHC testing. Of these, loss of MLH1 was noted in 8/9 (89%) tumors and loss of MSH2/MSH6 was noted in 1/9 (11%). Two patients had normal gene MLH1 gene sequencing, 2 patients
S193
declined further testing, and 2 patients were lost to follow-up. The 3 remaining patients have had genetic testing, but the results are pending at this time. Results will be available at the time of presentation. Conclusion: A high proportion of EC patients from ages 50 to 60 years had abnormal IHC testing (20%). The majority of their tumors had a loss of MLH1 expression which can either be due to a gene mutation or hypermethylation of the MLH1 gene promoter. Also, of these patients, only 1 patient had a personal history of cancer and only 2 patients had a family history of Lynch-associated malignancies. IHC screening of EC patients less than 60 years may be reasonable in those patients with a significant family or personal history of cancer.
doi:10.1016/j.ygyno.2012.01.027
12 Nanometastases of Endometrial Carcinoma to Sentinel Lymph Nodes: The Contribution of Pathologic Ultrastaging C. Kim, F. Khoury-Collado, J. Barlin, K. Park, D. Cassella, Y. Sonoda, M. Hensley, D. Chi, R. Barakat, N. Abu-Rustum. Memorial Sloan-Kettering Cancer Center, New York, NY. Objectives: To describe the incidence of nanometastases in sentinel lymph nodes (SLN) identified at surgical staging for endometrial carcinoma (EC) and to correlate it with depth of myoinvasion (DMI) and tumor grade. Methods: We reviewed all patients (pts) who underwent primary surgery for EC with successful mapping of at least one SLN at our institution from 9/2005-4/2011. The pathology protocol for SLN ultrastaging evaluation involved cutting an additional 2 adjacent 5um sections at each of two levels, 50-um apart, from each paraffin block lacking metastatic carcinoma appreciable in a routine section stained with hematoxylin and eosin (H&E). At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anti-cytokeratin AE1:AE3. Micrometastasis (MM) was defined as a focus of metastatic cancer N0.2 mm to 2 mm. Isolated tumor cells (ITC) were defined as metastasis measuring b0.2 mm. Cytokeratin positive cells (CKPC) included the presence of single cytokeratin positive cells, the clinical significance of which is uncertain. We defined nanometastases as all cases of MM and ITC detected by pathologic ultrastaging. Results: We identified 401 pts with the following histologies: 319 (79.6%) endometrioid, 58 (14.4%) serous or clear cell, 16 (5.5%) carcinosarcoma, and 2 (0.5%) undifferentiated. There were 203 (50.5%) pts with no myometrial invasion, 145 (36.2%) with b50%, and 53 (13.2%) with ≥50%. SLN was positive for metastatic disease on initial routine H&E in 27/ 401 (6.7%). Ultrastaging detected an additional 9 (2.2%) pts with nanometastases in their SLN that would have been missed otherwise including: 2 MM, 7 ITCu (only found on ultrastaging). In 4 pts, pathologists used a combination of ultrastaging and H&E to confirm metastatic isolated tumor cells in SLN (ITCc). The total incidence of nanometastases was 13/401 (3.2%). There were 10 (2.5%) CKPC pts. The incidence of nanometastases were 1.9%, 2.2%, and 3.1% in grade 1, 2, and 3 tumors, respectively. There was an additional 4.8% incidence of nanometasasis in tumors with ≤50% myoinvasion. Conclusion: SLN mapping with pathologic ultrastaging in endometrial cancer provides an opportunity to detect nanometastases, which would otherwise be undetected with routine pathologic evaluation. The significance of this finding in pts is not yet known. These data support the incorporation of pathologic ultrastaging and SLN mapping algorithm in endometrial cancer surgery especially for the presumed low-risk group (≤50% myoinvasion). doi:10.1016/j.ygyno.2012.01.028