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33. Is there a need for expert opinion in difficult cases of maliganant mesothelioma?
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PATHOLOGY 2012 ABSTRACT SUPPLEMENT
18q11.2 break apart probe showed a rearrangement in the majority of tumour cells, consistent with synovial sarcoma. Conclusions: Although its occurrence is rare, synovial sarcoma should be considered in the differential diagnosis of spindle cell neoplasms of the mediastinum. The distinction can be challenging, especially on a small biopsy or fine needle aspiration biopsy specimens alone, however the use of immunohistochemistry and molecular cytogenetics has enabled confirmation of the diagnosis in more than 90% of the cases. 33. IS THERE A NEED FOR EXPERT OPINION IN DIFFICULT CASES OF MALIGANANT MESOTHELIOMA? M. Ely, K. Griggs, D. W. Henderson, S. Klebe SA Pathology at Flinders Medical Centre and Flinders University, Adelaide, SA, Australia Background: Malignant mesothelioma is an aggressive tumour of serosal membranes, caused by inhalation of asbestos fibres. Diagnosis can be problematic because diagnostic biopsies are often small and immunohistochemical markers are of limited use for distinguishing benign from malignant mesothelial proliferations. Difficult cases are routinely referred for ‘expert opinion’. Aim: To determine the proportion of cases referred for expert opinion, where the opinion provided differed significantly from the original diagnosis. Methods: Cases of suspected mesothelioma referred for expert opinion were retrieved from the departmental files of Flinders Medical Centre, SA, for the 10 year period from 2000 to 2010. Original diagnoses were obtained from the referring pathology laboratories. Available original diagnoses and expert opinions were assigned categories (probable/definite) based on stated certainty of diagnosis. Results: A total of 275 cases were retrieved. For 13 of these, an original diagnosis was not retrieved. Of the 262 remaining cases, 136 were originally diagnosed as probable/definite malignant mesothelioma. Expert opinion agreed with that diagnosis for 117 cases, but the diagnosis for nine (7%) cases changed to probable/definite benign. Of the 39 cases that were originally diagnosed as probable/definite benign, 26 were considered benign by expert opinion, but 11 (28%) were diagnosed as probable/ definite malignant mesothelioma. For 73 cases no preferred diagnosis (indeterminate benign/malignant) had been made by the referring laboratory; of these 51 (70%) were considered probable/definite mesothelioma by expert opinion. Conclusions: These figures suggest that expert opinion can significantly differ from an original diagnosis, indicating a need for such a service. Presumably this reflects the rarity of such cases in most laboratories, in contrast to more extensive experience of an expert. 34. PREDICTION OF OUTCOME OF EARLY LUMINAL BREAST CANCER IS IMPROVED USING A BIOMARKER PANEL WHICH INCLUDES KI-67 AND P53 E. K. A. Millar1,2, P. H. Graham3, S. A. O’Toole1,4, L. Browne3, A. Boulghourjian1, C. M. McNeil1,5, J. H. Kearsley3, G. Papadatos6, G. Delaney7, C. Fox8, E. Nasser8, A. Capp9, R. L. Sutherland1 1 Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, 2Department of Anatomical Pathology, SEALS, St George Hospital Kogarah, 3Department of Radiation Oncology, Cancer Care Centre, St George Hospital Kogarah, 4Department of Diagnostic Oncology and Tissue Pathology, Royal Prince Alfred
Pathology (2012), 44(S1)
Hospital, 5Department of Medical Oncology Royal Prince Alfred Hospital, 6Macarthur Cancer Therapy Centre, 7Department of Radiation Oncology, Liverpool Hospital, 8Department of Radiation Oncology, Wollongong Hospital, and 9Department of Radiation Oncology, Mater Misericordiae Hospital, Newcastle, NSW, Australia Aim: To determine whether immunohistochemical (IHC) assessment of Ki-67 and p53 improves prognostication of luminal breast cancer after breast-conserving therapy (BCT). Methods: 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. Luminal tumours were classified as luminal A (LA): ERþ and/or PRþ, Ki-67 low, p53–, HER2–; or Luminal B (LB): ERþ and/or PRþ, Ki-67 high and/or p53þ and/or HER2þ. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis free survival (DMFS) and breast cancer specific survival (BCSS). Results: Seventy-three patients previously LA were re-classified as LB: a greater than four-fold increase (4.6% to 19.3%), compared to ER, PR, HER2 alone. In multivariate analysis the LB signature independently predicted LRR (HR 3.612, 95%CI 1.555–8.340, p ¼ 0.003), DMFS (HR 3.023, 95%CI 1.501–6.087, p ¼ 0.002) and BCSS (HR 3.617, 95%CI 1.629–8.031, p ¼ 0.002). Conclusions: The prognostic evaluation of luminal breast cancer is improved using a marker panel which includes Ki-67 and p53. This may help better define a group of poor prognosis ERþ patients with a greater probability of failure with endocrine therapy. 35. HEDGEHOG OVEREXPRESSION IS REGULATED BY STROMAL INTERACTIONS AND PREDICTS FOR POOR OUTCOME IN INVASIVE DUCTAL CARCINOMA Sandra O’Toole1, Dorothy Machakel1, Ewan Millar1, Radhika Nair1, Caroline Cooper2, Min Ru Qiu3, Duncan McLeod4, Robert Sutherland1, Neil Watkins5, Alexander Swarbrick1 1 Garvan Institute, 2Royal Prince Alfred Hospital, 3St Vincents Hospital, 4ICPMR, Sydney, NSW, and 5Monash Institute of Medical Research, Clayton, Vic, Australia Hedgehog (Hh) signalling plays an important role in a number of malignancies, yet its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma (IDC) of the breast, we found that expression of Hh ligand was associated with increased risk of metastasis, breast cancer specific death and the basal-like phenotype. A paracrine signature, encompassing high epithelial Hh ligand and high stromal Gli1 was an independent predictor for overall survival in multivariate analysis. In two independent histological progression series (n ¼ 301), Hh expression increased with atypia. Hh ligand overexpression in a mouse model of basal breast cancer, increased growth, induced a poorly differentiated phenotype, accelerated metastasis and reduced survival. A stromal requirement for these effects was supported by the lack of similar Hh-mediated changes in vitro, and by stromal-specific expression of Hh target genes in vivo. Furthermore, inhibition of Hh ligand with a monoclonal antibody (5E1) inhibited tumour growth and metastasis. These data suggest epithelial-stromal Hh signalling, driven by ligand expression in carcinoma cells, promotes breast cancer growth and metastasis. Blockade of Hh ligand activity may represent a novel therapeutic approach in metastatic breast cancer.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
PATHOLOGY 2012 ABSTRACT SUPPLEMENT
18q11.2 break apart probe showed a rearrangement in the majority of tumour cells, consistent with synovial sarcoma. Conclusions: Although its occurrence is rare, synovial sarcoma should be considered in the differential diagnosis of spindle cell neoplasms of the mediastinum. The distinction can be challenging, especially on a small biopsy or fine needle aspiration biopsy specimens alone, however the use of immunohistochemistry and molecular cytogenetics has enabled confirmation of the diagnosis in more than 90% of the cases. 33. IS THERE A NEED FOR EXPERT OPINION IN DIFFICULT CASES OF MALIGANANT MESOTHELIOMA? M. Ely, K. Griggs, D. W. Henderson, S. Klebe SA Pathology at Flinders Medical Centre and Flinders University, Adelaide, SA, Australia Background: Malignant mesothelioma is an aggressive tumour of serosal membranes, caused by inhalation of asbestos fibres. Diagnosis can be problematic because diagnostic biopsies are often small and immunohistochemical markers are of limited use for distinguishing benign from malignant mesothelial proliferations. Difficult cases are routinely referred for ‘expert opinion’. Aim: To determine the proportion of cases referred for expert opinion, where the opinion provided differed significantly from the original diagnosis. Methods: Cases of suspected mesothelioma referred for expert opinion were retrieved from the departmental files of Flinders Medical Centre, SA, for the 10 year period from 2000 to 2010. Original diagnoses were obtained from the referring pathology laboratories. Available original diagnoses and expert opinions were assigned categories (probable/definite) based on stated certainty of diagnosis. Results: A total of 275 cases were retrieved. For 13 of these, an original diagnosis was not retrieved. Of the 262 remaining cases, 136 were originally diagnosed as probable/definite malignant mesothelioma. Expert opinion agreed with that diagnosis for 117 cases, but the diagnosis for nine (7%) cases changed to probable/definite benign. Of the 39 cases that were originally diagnosed as probable/definite benign, 26 were considered benign by expert opinion, but 11 (28%) were diagnosed as probable/ definite malignant mesothelioma. For 73 cases no preferred diagnosis (indeterminate benign/malignant) had been made by the referring laboratory; of these 51 (70%) were considered probable/definite mesothelioma by expert opinion. Conclusions: These figures suggest that expert opinion can significantly differ from an original diagnosis, indicating a need for such a service. Presumably this reflects the rarity of such cases in most laboratories, in contrast to more extensive experience of an expert. 34. PREDICTION OF OUTCOME OF EARLY LUMINAL BREAST CANCER IS IMPROVED USING A BIOMARKER PANEL WHICH INCLUDES KI-67 AND P53 E. K. A. Millar1,2, P. H. Graham3, S. A. O’Toole1,4, L. Browne3, A. Boulghourjian1, C. M. McNeil1,5, J. H. Kearsley3, G. Papadatos6, G. Delaney7, C. Fox8, E. Nasser8, A. Capp9, R. L. Sutherland1 1 Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, 2Department of Anatomical Pathology, SEALS, St George Hospital Kogarah, 3Department of Radiation Oncology, Cancer Care Centre, St George Hospital Kogarah, 4Department of Diagnostic Oncology and Tissue Pathology, Royal Prince Alfred
Pathology (2012), 44(S1)
Hospital, 5Department of Medical Oncology Royal Prince Alfred Hospital, 6Macarthur Cancer Therapy Centre, 7Department of Radiation Oncology, Liverpool Hospital, 8Department of Radiation Oncology, Wollongong Hospital, and 9Department of Radiation Oncology, Mater Misericordiae Hospital, Newcastle, NSW, Australia Aim: To determine whether immunohistochemical (IHC) assessment of Ki-67 and p53 improves prognostication of luminal breast cancer after breast-conserving therapy (BCT). Methods: 498 patients with invasive breast cancer from a randomised trial of BCT with or without tumour bed radiation boost were assessed using IHC. Luminal tumours were classified as luminal A (LA): ERþ and/or PRþ, Ki-67 low, p53–, HER2–; or Luminal B (LB): ERþ and/or PRþ, Ki-67 high and/or p53þ and/or HER2þ. Kaplan-Meier and Cox proportional hazards methodology were used to ascertain relationships to ispilateral breast tumour recurrence (IBTR), locoregional recurrence (LRR), distant metastasis free survival (DMFS) and breast cancer specific survival (BCSS). Results: Seventy-three patients previously LA were re-classified as LB: a greater than four-fold increase (4.6% to 19.3%), compared to ER, PR, HER2 alone. In multivariate analysis the LB signature independently predicted LRR (HR 3.612, 95%CI 1.555–8.340, p ¼ 0.003), DMFS (HR 3.023, 95%CI 1.501–6.087, p ¼ 0.002) and BCSS (HR 3.617, 95%CI 1.629–8.031, p ¼ 0.002). Conclusions: The prognostic evaluation of luminal breast cancer is improved using a marker panel which includes Ki-67 and p53. This may help better define a group of poor prognosis ERþ patients with a greater probability of failure with endocrine therapy. 35. HEDGEHOG OVEREXPRESSION IS REGULATED BY STROMAL INTERACTIONS AND PREDICTS FOR POOR OUTCOME IN INVASIVE DUCTAL CARCINOMA Sandra O’Toole1, Dorothy Machakel1, Ewan Millar1, Radhika Nair1, Caroline Cooper2, Min Ru Qiu3, Duncan McLeod4, Robert Sutherland1, Neil Watkins5, Alexander Swarbrick1 1 Garvan Institute, 2Royal Prince Alfred Hospital, 3St Vincents Hospital, 4ICPMR, Sydney, NSW, and 5Monash Institute of Medical Research, Clayton, Vic, Australia Hedgehog (Hh) signalling plays an important role in a number of malignancies, yet its clinical significance in breast cancer is unclear. In a cohort of 279 patients with invasive ductal carcinoma (IDC) of the breast, we found that expression of Hh ligand was associated with increased risk of metastasis, breast cancer specific death and the basal-like phenotype. A paracrine signature, encompassing high epithelial Hh ligand and high stromal Gli1 was an independent predictor for overall survival in multivariate analysis. In two independent histological progression series (n ¼ 301), Hh expression increased with atypia. Hh ligand overexpression in a mouse model of basal breast cancer, increased growth, induced a poorly differentiated phenotype, accelerated metastasis and reduced survival. A stromal requirement for these effects was supported by the lack of similar Hh-mediated changes in vitro, and by stromal-specific expression of Hh target genes in vivo. Furthermore, inhibition of Hh ligand with a monoclonal antibody (5E1) inhibited tumour growth and metastasis. These data suggest epithelial-stromal Hh signalling, driven by ligand expression in carcinoma cells, promotes breast cancer growth and metastasis. Blockade of Hh ligand activity may represent a novel therapeutic approach in metastatic breast cancer.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.