- Email: [email protected]
39. Concordance of HER2 expression in primary and metastatic sites of gastric and gastro- oesophageal junction cancers
ABSTRACTS
in maximum extent and/or in deep-seated locations (excluding retroperitoneal cases) were included. FISH analysis was performed using in-house CDK4/MDM2/CEP12 probes. The clinical, radiological and pathological features of all cases with CDK4/MDM2 amplification were reviewed. Results: 81 cases were identified including 51 (63%) males and 30 females (37%) with a median age of 60 years (range 24–83). The most common site was the thigh (n ¼ 20). FISH analysis was attempted in 77 (95%) cases and karyotyping in 4 (5%). Cytogenetic analysis could not be performed in 4 (5%) cases due to technical factors. Two (3%) cases showed dual MDM2/CDK4 amplification and 2 (3%) showed MDM2 amplification alone. All were deep seated with a median size of 95 mm (range 35–160 mm). Two had unusual radiological findings (intermediate signal intensity on MRI). Retrospective slide review confirmed the absence of diagnostic features of WD-LLLPS. Two cases showed marked degenerative changes and one showed prominent lymphocytic inflammation. Conclusions: The incidence of MDM2/CDK4 amplification was reassuringly low (5%) in this cohort of LN, despite their large and/ or deep-seated nature. Features that may suggest a potentially more aggressive neoplasm include unusual radiological findings, degenerative changes and prominent inflammation.
39. CONCORDANCE OF HER2 EXPRESSION IN PRIMARY AND METASTATIC SITES OF GASTRIC AND GASTRO- OESOPHAGEAL JUNCTION CANCERS D. D. Wong1, W. B. de Boer1,2, M. Platten1 and M. P. Kumarasinghe1,2 1Anatomical Pathology, PathWest Laboratory Medicine, and 2School of Pathology and Laboratory Medicine, University of WA, WA, Australia Background: HER2 is known to be overexpressed in a subset of patients with gastric and gastro-oesophageal junction (G/GOJ) adenocarcinomas. Such patients with advanced/metastatic disease may benefit from Herceptin therapy. However, there are very limited data currently available regarding concordance of HER2 expression between primary and metastatic sites. Aims: To compare HER2 status in primary and metastatic sites of G/GOJ cancers in a single centre. Methods: 124 samples from 40 cases with paired primary and metastatic tumours were tested for HER2 status, assessed by both immunohistochemistry (IHC) for protein expression and silver in situ hybridisation (SISH) for gene amplification. IHC was scored according to the modified criteria of Hoffman et al. for endoscopic biopsies. An average of six or more signals per nucleus, counting at least 20 malignant cells was considered amplification on SISH. Results: Primary site samples tested included endoscopic biopsies (n ¼ 26) and resections (n ¼ 33). Metastatic site samples included lymph nodes (n ¼ 27), effusions (n ¼ 17) and miscellaneous sites (n ¼ 9). Of 38 (95%) concordant cases, 36 were negative and 2 were positive for HER2 by both IHC and SISH. Of the 2 (5%) discordant cases, one showed positive IHC (not SISH) in only one of 3 primary endoscopic biopsies and the other showed heterogeneous positivity in the resection specimen with both IHC and SISH but was negative in the primary site biopsy and the ascitic fluid. Conclusions: The majority of cases (95%) showed concordance suggesting HER2 testing of primary and metastatic sites are equally valid. Few cases of true HER2 expression may be missed by testing one site alone.
S119
40. HER2 EXPRESSION IN MALIGNANT EFFUSIONS OF METASTATIC GASTRIC CARCINOMA D. D. Wong1, W. B. de Boer1,2, M. Platten1, V. Y. Jo3, E. S. Cibas3 and M. P. Kumarasinghe1,2 1Anatomical Pathology, PathWest Laboratory Medicine, 2School of Pathology and Laboratory Medicine, University of WA, WA, Australia, and 3Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Background: Advanced gastric carcinoma commonly spreads to the peritoneum producing ascites. Such patients may require assessment of HER2 status on ascitic fluid prior to being considered for Herceptin. Aims: To investigate the feasibility of HER2 assessment in malignant effusions by immunohistochemistry (IHC) and silver in situ hybridisation (SISH). Methods: Cell block preparations from 44 malignant effusions in patients with a diagnosis of metastatic gastric carcinoma were examined. IHC was scored according to the modified criteria of Hoffman et al. for endoscopic biopsies. An average of 6 or more signals per nucleus, counting at least 20 malignant cells was considered amplification on SISH. Results: Peritoneal cytology showed a poorly cohesive, single cell pattern in 29 cases, aggregates in 7 and a mixed pattern in 8. Six cases showed an IHC 2þ or 3þ reaction. The staining pattern was membranous but more granular compared to histology. Two cases showed HER2 amplification. HER2 signals were satisfactorily identified in both the malignant cells and background mesothelial cells in all but one of the samples. Difficulties were encountered in distinguishing malignant cells from reactive mesothelial and inflammatory cells (12 cases). These cases generally showed a poorly cohesive, single cell pattern without frank pleomorphism. Furthermore, it was difficult to apply the modified criteria of Hoffman et al. in the absence of clusters. Conclusions: Only 4.5% of cases showed IHC 2þ/3þ with gene amplification, lower than reported in histological samples. This may be related to the predominance of a poorly cohesive, single cell pattern (66%). IHC staining pattern was membranous but more granular compared to histology. This study supports the feasibility of HER2 assessment in ascitic fluid in metastatic gastric carcinoma. However, there are difficulties and the technique needs further improvement and validation for use in clinical practice. 41. CASE REPORT: TELANGIECTATIC OSTEOSARCOMA OF THE LEFT HUMERUS IN A 13 YEAR OLD GIRL Yanling Yang1, Lynnette Moore1, Juliet Kaye2 and Jill Lipsett1 1SA Pathology, Department of Surgical Pathology, Women’s and Children’s Hospital, North Adelaide, and 2Department of Radiology, Women’s and Children’s Hospital, North Adelaide, SA, Australia Telangiectatic osteosarcoma is a rare variant, representing around 3% of osteosarcomas overall. The main differential radiographically, grossly and on histology is with aneurysmal bone cyst and both these lesions tend to occur in the metaphysis of long bones with a peak incidence in the 2nd decade. We present the case of a 13-year-old girl who attended the Women’s and Children’s Hospital, Adelaide with left upper arm pain for 4 weeks after a fall in 2012. An X-ray showed a lytic destructive lesion of the proximal left humerus while magnetic resonance imaging revealed features
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
in maximum extent and/or in deep-seated locations (excluding retroperitoneal cases) were included. FISH analysis was performed using in-house CDK4/MDM2/CEP12 probes. The clinical, radiological and pathological features of all cases with CDK4/MDM2 amplification were reviewed. Results: 81 cases were identified including 51 (63%) males and 30 females (37%) with a median age of 60 years (range 24–83). The most common site was the thigh (n ¼ 20). FISH analysis was attempted in 77 (95%) cases and karyotyping in 4 (5%). Cytogenetic analysis could not be performed in 4 (5%) cases due to technical factors. Two (3%) cases showed dual MDM2/CDK4 amplification and 2 (3%) showed MDM2 amplification alone. All were deep seated with a median size of 95 mm (range 35–160 mm). Two had unusual radiological findings (intermediate signal intensity on MRI). Retrospective slide review confirmed the absence of diagnostic features of WD-LLLPS. Two cases showed marked degenerative changes and one showed prominent lymphocytic inflammation. Conclusions: The incidence of MDM2/CDK4 amplification was reassuringly low (5%) in this cohort of LN, despite their large and/ or deep-seated nature. Features that may suggest a potentially more aggressive neoplasm include unusual radiological findings, degenerative changes and prominent inflammation.
39. CONCORDANCE OF HER2 EXPRESSION IN PRIMARY AND METASTATIC SITES OF GASTRIC AND GASTRO- OESOPHAGEAL JUNCTION CANCERS D. D. Wong1, W. B. de Boer1,2, M. Platten1 and M. P. Kumarasinghe1,2 1Anatomical Pathology, PathWest Laboratory Medicine, and 2School of Pathology and Laboratory Medicine, University of WA, WA, Australia Background: HER2 is known to be overexpressed in a subset of patients with gastric and gastro-oesophageal junction (G/GOJ) adenocarcinomas. Such patients with advanced/metastatic disease may benefit from Herceptin therapy. However, there are very limited data currently available regarding concordance of HER2 expression between primary and metastatic sites. Aims: To compare HER2 status in primary and metastatic sites of G/GOJ cancers in a single centre. Methods: 124 samples from 40 cases with paired primary and metastatic tumours were tested for HER2 status, assessed by both immunohistochemistry (IHC) for protein expression and silver in situ hybridisation (SISH) for gene amplification. IHC was scored according to the modified criteria of Hoffman et al. for endoscopic biopsies. An average of six or more signals per nucleus, counting at least 20 malignant cells was considered amplification on SISH. Results: Primary site samples tested included endoscopic biopsies (n ¼ 26) and resections (n ¼ 33). Metastatic site samples included lymph nodes (n ¼ 27), effusions (n ¼ 17) and miscellaneous sites (n ¼ 9). Of 38 (95%) concordant cases, 36 were negative and 2 were positive for HER2 by both IHC and SISH. Of the 2 (5%) discordant cases, one showed positive IHC (not SISH) in only one of 3 primary endoscopic biopsies and the other showed heterogeneous positivity in the resection specimen with both IHC and SISH but was negative in the primary site biopsy and the ascitic fluid. Conclusions: The majority of cases (95%) showed concordance suggesting HER2 testing of primary and metastatic sites are equally valid. Few cases of true HER2 expression may be missed by testing one site alone.
S119
40. HER2 EXPRESSION IN MALIGNANT EFFUSIONS OF METASTATIC GASTRIC CARCINOMA D. D. Wong1, W. B. de Boer1,2, M. Platten1, V. Y. Jo3, E. S. Cibas3 and M. P. Kumarasinghe1,2 1Anatomical Pathology, PathWest Laboratory Medicine, 2School of Pathology and Laboratory Medicine, University of WA, WA, Australia, and 3Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA Background: Advanced gastric carcinoma commonly spreads to the peritoneum producing ascites. Such patients may require assessment of HER2 status on ascitic fluid prior to being considered for Herceptin. Aims: To investigate the feasibility of HER2 assessment in malignant effusions by immunohistochemistry (IHC) and silver in situ hybridisation (SISH). Methods: Cell block preparations from 44 malignant effusions in patients with a diagnosis of metastatic gastric carcinoma were examined. IHC was scored according to the modified criteria of Hoffman et al. for endoscopic biopsies. An average of 6 or more signals per nucleus, counting at least 20 malignant cells was considered amplification on SISH. Results: Peritoneal cytology showed a poorly cohesive, single cell pattern in 29 cases, aggregates in 7 and a mixed pattern in 8. Six cases showed an IHC 2þ or 3þ reaction. The staining pattern was membranous but more granular compared to histology. Two cases showed HER2 amplification. HER2 signals were satisfactorily identified in both the malignant cells and background mesothelial cells in all but one of the samples. Difficulties were encountered in distinguishing malignant cells from reactive mesothelial and inflammatory cells (12 cases). These cases generally showed a poorly cohesive, single cell pattern without frank pleomorphism. Furthermore, it was difficult to apply the modified criteria of Hoffman et al. in the absence of clusters. Conclusions: Only 4.5% of cases showed IHC 2þ/3þ with gene amplification, lower than reported in histological samples. This may be related to the predominance of a poorly cohesive, single cell pattern (66%). IHC staining pattern was membranous but more granular compared to histology. This study supports the feasibility of HER2 assessment in ascitic fluid in metastatic gastric carcinoma. However, there are difficulties and the technique needs further improvement and validation for use in clinical practice. 41. CASE REPORT: TELANGIECTATIC OSTEOSARCOMA OF THE LEFT HUMERUS IN A 13 YEAR OLD GIRL Yanling Yang1, Lynnette Moore1, Juliet Kaye2 and Jill Lipsett1 1SA Pathology, Department of Surgical Pathology, Women’s and Children’s Hospital, North Adelaide, and 2Department of Radiology, Women’s and Children’s Hospital, North Adelaide, SA, Australia Telangiectatic osteosarcoma is a rare variant, representing around 3% of osteosarcomas overall. The main differential radiographically, grossly and on histology is with aneurysmal bone cyst and both these lesions tend to occur in the metaphysis of long bones with a peak incidence in the 2nd decade. We present the case of a 13-year-old girl who attended the Women’s and Children’s Hospital, Adelaide with left upper arm pain for 4 weeks after a fall in 2012. An X-ray showed a lytic destructive lesion of the proximal left humerus while magnetic resonance imaging revealed features
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.