- Email: [email protected]
MUC2 staining is not useful to predict subsequent development of intestinal metaplasia in oesophageal biopsies
ABSTRACTS
Methods: De facto small biopsies were made by creating a TMA from consecutive cases of resected lung cancer. Immunohistochemistry was performed on these biopsies and compared to the final histology from the excision specimens. Results: TTF-1 stained 129 of 151 ACs (85.4%) and 12 of 70 (17.1%) SCCs. Napsin A stained 124 of 151 ACs (82.1%) and 9 of 70 (12.9%) SCCs. P63 stained 5 of 151 ACs (3.3%) and 58 of 70 SCCs (82.9%). CK5/6 stained 7 of 151 ACs (4.6%) and 62 of 70 SCCs (88.6%). The presence of one or both of the adenocarcinoma or squamous markers resulted in accurate classification in 183 of 223 (82.1%) cases. Thirty-seven cases showed positive staining for both adenocarcinoma and squamous carcinoma markers. Slides were unavailable for three cases. Conclusion: We conclude that immunohistochemistry may assist subclassification of poorly differentiated NSCLCs in small biopsies, but is not always definitive. IMMUNOHISTOCHEMISTRY FIRST AS A SCREENING STRATEGY FOR TARGETED THERAPY OF LUNG CANCER Mahtab Farzin1, Loretta Sioson1, Adele Clarkson1, Bing Yu2, Ronald Trent2, Chiu Chin Ng2, Christina Selinger2, K. T. George1, Wendy Cooper3, Sandra O’Toole3*, Anthony Gill1* 1 Department of Anatomical Pathology, Royal North Shore Hospital, 2Dept of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, and 3Departments of Tissue Oncology and Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; *these authors contributed equally Activating mutations of EGFR and the EML4-ALK translocation predict sensitivity to specific targeted therapies for lung cancer. Currently testing is generally performed by direct sequencing and fluorescence in situ hybridisation (FISH) respectively. We trialled immunohistochemistry with mutation-specific antibodies for EGFR exon 19 (Cell Signalling catalogue 2085S) and EGFR EXON 21 (Cell Signalling catalogue 3197S) and ALK (Novacastra, clone 5A4) as screening tests for these targets. Staining was performed on a TMA containing 231 resected nonsmall cell carcinomas including 151 adenocarcinomas. Six showed positive staining for EGFR exon 19 mutation, six for EGFR exon 21 and four for ALK. All 16 demonstrated adenocarcinoma histology and were subsequently shown to harbour the predicted activating mutation or translocation by sequencing and FISH. Although our study was not intended or designed to assess the sensitivity of immunohistochemistry, we conclude that immunohistochemistry is highly specific for these targets. We propose that immunohistochemistry may be used to triage all patients (including low risk patients) for formal sequencing or FISH analysis. If our results are confirmed by others, it may be appropriate to offer targeted therapies to those with positive immunohistochemistry and reserve sequencing/FISH for those cases negative by immunohistochemistry but considered to have a high clinical probability of these abnormalities. MATERNAL BREAST CARCINOMA METASTASES TO THE PLACENTA: A CASE REPORT AND LITERATURE REVIEW Choon Yan Ho, Lai Meng Looi Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
S61
Pregnancy associated with malignancy and placental metastasis is uncommon. Seventy-three cases of placental metastases have been reported in the English literature. The most common placental metastases are from melanoma, followed by haematological malignancies. We report a case of maternal breast malignancy with placental micrometastasis despite an unremarkable gross placental appearance in a 42-year-old Chinese lady. She was diagnosed with infiltrating ductal carcinoma grade 3 in 2007 and underwent surgery and chemoradiation. She presented recently with an unplanned pregnancy and opted for termination of pregnancy. The placenta was grossly normal. However, microscopy revealed infiltration of chorionic villi by malignant epithelial cells which were immunopositive for ER and PR; negative for b-hCG, S-100 protein and HMB-45. The amniotic membranes, umbilical cord and major fetal organs were unremarkable. This case highlights the importance of examination of the placenta in maternal malignancies, as findings have a bearing on management of the patient and newborn (in the case of term pregnancy). Other than microscopy for the presence of malignant cells in the intervillous space, one needs to scrutinise for malignant villous invasion which is associated with fetal metastasis. This warrants closer and longer followup for the infant to detect systemic involvement by malignancy. ERG IMMUNOSTAINING IS HIGHLY SPECIFIC FOR PROSTATIC ADENOCARCINOMA Michelle Houang, Loretta Siosin, Nicole Watson, Adele Clarkson, Anthony Gill Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia Aims: Immunohistochemistry for ERG has been reported to be highly sensitive and specific for the TMPRSS2-ERG fusion oncogene. This fusion oncogene has been found in 50–70% of prostate cancers in screened populations but rarely to never in benign disease. We sought to assess the sensitivity and specificity of immunohistochemistry for ERG for the diagnosis of prostate carcinoma in an Australian population. Methods: A TMA was constructed containing material from 283 consecutive prostatic adenocarcinomas from radical prostatectomies. Immunohistochemistry was performed with a mouse monoclonal antibody directed against ERG (clone 9FY Biocare Medical, USA). Results: ERG staining was positive in 146 adenocarcinomas (51.5%). There was no staining of benign glands (specificity 100%). Commonly high grade PIN (HGPIN) adjacent to adenocarcinoma showed positive staining, but in only two cases was there positive staining in PIN without there being ERG positive carcinoma present in the same TMA core. Conclusions: ERG shows a sensitivity of 51.5% and a remarkable specificity of 100% for the diagnosis of prostatic adenocarcinoma versus benign glands. ERG positive PIN is almost always associated with invasive adenocarcinoma in the same core biopsy. Immunohistochemistry for ERG may therefore have significant role in the pathological differential diagnosis of difficult prostate biopsies. MUC2 STAINING IS NOT USEFUL TO PREDICT SUBSEQUENT DEVELOPMENT OF INTESTINAL METAPLASIA IN OESOPHAGEAL BIOPSIES P. Irandoost, L. Siosson, A. Clarkson, A. J. Gill Royal North Shore Hospital, Sydney, NSW, Australia Aims: It has recently been postulated that goblet cells in the oesophagus eventually develop from a field of metaplastic
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
S62
PATHOLOGY 2012 ABSTRACT SUPPLEMENT
columnar cells with MUC2 positivity. The aim of our study was to assess whether MUC2 positivity in columnar cells predicts subsequent identification of goblet cells. Methods: Twenty-two study cases were found (over 1998–2011) with intestinal metaplasia that had initial negative biopsies. MUC2 staining was performed on a positive and a negative biopsy from every case and compared with 29 control cases that never had goblet cells on multiple subsequent biopsies. Results: All goblet cells and the majority of columnar cells directly in the vicinity of goblet cells (17/22 cases) showed MUC2 staining. This was less significant in the columnar cells away from goblet cells with only 6/22 cases showing positive staining. Fifteen of 22 (68%) cases with intestinal metaplasia showed some positive MUC2 staining on their earlier negative biopsies. Fourteen of 29 (48%) individuals who never had goblet cells on subsequent biopsies showed positive MUC2 staining. Conclusion: Although the rate of MUC2 positivity was slightly higher on initial negative biopsies of individuals with intestinal metaplasia, our findings do not suggest that routine staining for MUC2 will be useful to predict subsequent diagnosis of intestinal metaplasia in columnar lined oesophagus. References 1. McIntire M, Soucy G, Vaughan T, et al. MUC2 is a highly specific marker of goblet cell metaplasia in the distal oesophagus and the gastrooesophageal junction. Am J Surg Pathol 2011; 35: 1007–13. 2. Hahn H, Blount PL, Ayub K, et al. Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the oesophagus. Am J Surg Pathol 2009; 33: 1006– 15. 3. Chandrasoma P, Wijetunge S, DeMeester S, et al. Columnar-lined oesophagus without intestinal metaplasia has no proven risk of adenocarcinoma. Am J Surg Pathol 2012; 36: 1–7. 4. Niv Y, Fass R. The role of mucin in GERD and its complications. Nat Rev Gastroenterol Hepatol 2011; 9: 55–9.
‘GIVE THEM AN INCH. . .’: DABIGATRAN PRESCRIPTION IN VICTORIA Sueh-li Lim, Shaun Fleming, Ellen Maxwell Melbourne Pathology, Collingwood, Vic, Australia Background: Dabigatran is a direct thrombin inhibitor recently available through a physician familiarisation program (PFP) for prophylaxis of patients with non-valvular atrial fibrillation. The PFP was supported by pharmaceutical industry sponsored education. National and international reports of bleeding associated with this drug suggest inappropriate patient selection. Objectives: To compare the characteristics of local patients prescribed dabigatran for the prevention of stroke with the RE-LY study population. Methods: Retrospective analysis of patients exiting our oral anticoagulant service, transferred to dabigatran from warfarin, between June and November 2011 inclusive. Results: 362 patients were known to be prescribed dabigatran. They were on average older than those of the RE-LY study (median age 78 versus 71 years), included those with significant renal impairment eGFR <50 mL/min/1.73m2 (51/362, 14%) and patients in whom renal function (45/362, 12%) was not assessed. Two hundred and thirteen patients (58.8%) were transferred to dabigatran despite high quality anticoagulant management, defined as a time in therapeutic range (TTR) >65%; average TTR was 70% compared to 64% in the RE-LY study. Mild thrombocytopenia and concurrent antiplatelet drugs were noted in 12% and 15%, respectively. Conclusions: Our study confirms prescription of dabigatran to a local population dissimilar to the RE-LY cohort.
Pathology (2012), 44(S1)
IMP3 STAINING IS NOT A USEFUL MARKER FOR ADRENOCORTICAL CARCINOMA H. M. Manuchehri, A. Clarkson, L. Siosson, A. J. Gill Royal North Shore Hospital, Sydney, NSW, Australia Adrenocortical carcinoma (ACC) is a rare tumour with challenging pathological diagnosis. The Weiss scoring system which is based on the recognition of at least three of nine morphological parameters is the most widely used criteria. However the Weiss system is not entirely sensitive or specific, and some of the criteria are subjective and potentially problematic. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC. Alterations of the insulin-like growth factor-II (IGF-2) molecule seem to be promising particularly when used in conjunction with Ki67 index. The insulin-like growth factor-II mRNAbinding protein (IMP3) has been shown to be a useful marker of malignancy in multiple organs. We investigated IMP3 expression by immunohistochemistry in TMAs of 35 ACCs and 161 adrenal cortical adenomas. IMP3 immunoreactivity was seen in two (6%) ACC and in none of the adrenal cortical adenomas. We conclude that despite its high specificity for the diagnosis of malignancy in adrenal cortical neoplasms, its very low sensitivity means IMP3 overexpression is unlikely to be useful in the diagnostic setting. References 1. Findeis-Hosey JJ, H Xu H. The use of insulin like-growth factor II messenger RNA binding protein –3 in diagnostic pathology. Hum Pathol 2011; 42: 303– 14. 2. Volante M, Buttigliero C,Greco E, et al. Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 2008; 61: 787–93. 3. Soon PS, Gill AJ, Clarkson, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumours identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer 2009; 16: 573–83.
A REVIEW OF DIAGNOSTIC UTILITY OF P16INK4A IMMUNOSTAINING AS A MARKER OF HIGH-RISK HPV AND HIGH-GRADE CERVICAL INTRAEPITHELIAL NEOPLASIA Ali Moghimi, Simon Nazaretian Anatomical Pathology Department, The Royal Women’s Hospital, Parkville, Vic, Australia The most frequent type of cervical cancer is squamous-cell carcinoma which develops from cervical intraepithelial neoplasia (CIN) / squamous intraepithelial lesion (SIL). Its tumorigenesis is related to human papillomavirus (HPV). High-risk HPV is integrated into the genome and leads to tumour progression. Cytological screening leads to detection of precursors and their mimics. P16INK4a and Ki-67 immunohistochemistry assists in the histological differential diagnosis of precursors to reactive and metaplastic epithelium. P16INK4a has emerged as a valuable surrogate marker for high-risk HPV infection and shows increased immunoexpression with worsening grades of CIN. Numerous studies have supported its role in the detection of high-grade dysplasia and have lead to the use of p16INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16INK4a in everyday practice, including the problems in the interpretation of the patterns of immunostaining and standardisation of the p16INK4a scoring.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
Methods: De facto small biopsies were made by creating a TMA from consecutive cases of resected lung cancer. Immunohistochemistry was performed on these biopsies and compared to the final histology from the excision specimens. Results: TTF-1 stained 129 of 151 ACs (85.4%) and 12 of 70 (17.1%) SCCs. Napsin A stained 124 of 151 ACs (82.1%) and 9 of 70 (12.9%) SCCs. P63 stained 5 of 151 ACs (3.3%) and 58 of 70 SCCs (82.9%). CK5/6 stained 7 of 151 ACs (4.6%) and 62 of 70 SCCs (88.6%). The presence of one or both of the adenocarcinoma or squamous markers resulted in accurate classification in 183 of 223 (82.1%) cases. Thirty-seven cases showed positive staining for both adenocarcinoma and squamous carcinoma markers. Slides were unavailable for three cases. Conclusion: We conclude that immunohistochemistry may assist subclassification of poorly differentiated NSCLCs in small biopsies, but is not always definitive. IMMUNOHISTOCHEMISTRY FIRST AS A SCREENING STRATEGY FOR TARGETED THERAPY OF LUNG CANCER Mahtab Farzin1, Loretta Sioson1, Adele Clarkson1, Bing Yu2, Ronald Trent2, Chiu Chin Ng2, Christina Selinger2, K. T. George1, Wendy Cooper3, Sandra O’Toole3*, Anthony Gill1* 1 Department of Anatomical Pathology, Royal North Shore Hospital, 2Dept of Molecular and Clinical Genetics, Royal Prince Alfred Hospital, and 3Departments of Tissue Oncology and Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; *these authors contributed equally Activating mutations of EGFR and the EML4-ALK translocation predict sensitivity to specific targeted therapies for lung cancer. Currently testing is generally performed by direct sequencing and fluorescence in situ hybridisation (FISH) respectively. We trialled immunohistochemistry with mutation-specific antibodies for EGFR exon 19 (Cell Signalling catalogue 2085S) and EGFR EXON 21 (Cell Signalling catalogue 3197S) and ALK (Novacastra, clone 5A4) as screening tests for these targets. Staining was performed on a TMA containing 231 resected nonsmall cell carcinomas including 151 adenocarcinomas. Six showed positive staining for EGFR exon 19 mutation, six for EGFR exon 21 and four for ALK. All 16 demonstrated adenocarcinoma histology and were subsequently shown to harbour the predicted activating mutation or translocation by sequencing and FISH. Although our study was not intended or designed to assess the sensitivity of immunohistochemistry, we conclude that immunohistochemistry is highly specific for these targets. We propose that immunohistochemistry may be used to triage all patients (including low risk patients) for formal sequencing or FISH analysis. If our results are confirmed by others, it may be appropriate to offer targeted therapies to those with positive immunohistochemistry and reserve sequencing/FISH for those cases negative by immunohistochemistry but considered to have a high clinical probability of these abnormalities. MATERNAL BREAST CARCINOMA METASTASES TO THE PLACENTA: A CASE REPORT AND LITERATURE REVIEW Choon Yan Ho, Lai Meng Looi Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
S61
Pregnancy associated with malignancy and placental metastasis is uncommon. Seventy-three cases of placental metastases have been reported in the English literature. The most common placental metastases are from melanoma, followed by haematological malignancies. We report a case of maternal breast malignancy with placental micrometastasis despite an unremarkable gross placental appearance in a 42-year-old Chinese lady. She was diagnosed with infiltrating ductal carcinoma grade 3 in 2007 and underwent surgery and chemoradiation. She presented recently with an unplanned pregnancy and opted for termination of pregnancy. The placenta was grossly normal. However, microscopy revealed infiltration of chorionic villi by malignant epithelial cells which were immunopositive for ER and PR; negative for b-hCG, S-100 protein and HMB-45. The amniotic membranes, umbilical cord and major fetal organs were unremarkable. This case highlights the importance of examination of the placenta in maternal malignancies, as findings have a bearing on management of the patient and newborn (in the case of term pregnancy). Other than microscopy for the presence of malignant cells in the intervillous space, one needs to scrutinise for malignant villous invasion which is associated with fetal metastasis. This warrants closer and longer followup for the infant to detect systemic involvement by malignancy. ERG IMMUNOSTAINING IS HIGHLY SPECIFIC FOR PROSTATIC ADENOCARCINOMA Michelle Houang, Loretta Siosin, Nicole Watson, Adele Clarkson, Anthony Gill Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia Aims: Immunohistochemistry for ERG has been reported to be highly sensitive and specific for the TMPRSS2-ERG fusion oncogene. This fusion oncogene has been found in 50–70% of prostate cancers in screened populations but rarely to never in benign disease. We sought to assess the sensitivity and specificity of immunohistochemistry for ERG for the diagnosis of prostate carcinoma in an Australian population. Methods: A TMA was constructed containing material from 283 consecutive prostatic adenocarcinomas from radical prostatectomies. Immunohistochemistry was performed with a mouse monoclonal antibody directed against ERG (clone 9FY Biocare Medical, USA). Results: ERG staining was positive in 146 adenocarcinomas (51.5%). There was no staining of benign glands (specificity 100%). Commonly high grade PIN (HGPIN) adjacent to adenocarcinoma showed positive staining, but in only two cases was there positive staining in PIN without there being ERG positive carcinoma present in the same TMA core. Conclusions: ERG shows a sensitivity of 51.5% and a remarkable specificity of 100% for the diagnosis of prostatic adenocarcinoma versus benign glands. ERG positive PIN is almost always associated with invasive adenocarcinoma in the same core biopsy. Immunohistochemistry for ERG may therefore have significant role in the pathological differential diagnosis of difficult prostate biopsies. MUC2 STAINING IS NOT USEFUL TO PREDICT SUBSEQUENT DEVELOPMENT OF INTESTINAL METAPLASIA IN OESOPHAGEAL BIOPSIES P. Irandoost, L. Siosson, A. Clarkson, A. J. Gill Royal North Shore Hospital, Sydney, NSW, Australia Aims: It has recently been postulated that goblet cells in the oesophagus eventually develop from a field of metaplastic
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.
S62
PATHOLOGY 2012 ABSTRACT SUPPLEMENT
columnar cells with MUC2 positivity. The aim of our study was to assess whether MUC2 positivity in columnar cells predicts subsequent identification of goblet cells. Methods: Twenty-two study cases were found (over 1998–2011) with intestinal metaplasia that had initial negative biopsies. MUC2 staining was performed on a positive and a negative biopsy from every case and compared with 29 control cases that never had goblet cells on multiple subsequent biopsies. Results: All goblet cells and the majority of columnar cells directly in the vicinity of goblet cells (17/22 cases) showed MUC2 staining. This was less significant in the columnar cells away from goblet cells with only 6/22 cases showing positive staining. Fifteen of 22 (68%) cases with intestinal metaplasia showed some positive MUC2 staining on their earlier negative biopsies. Fourteen of 29 (48%) individuals who never had goblet cells on subsequent biopsies showed positive MUC2 staining. Conclusion: Although the rate of MUC2 positivity was slightly higher on initial negative biopsies of individuals with intestinal metaplasia, our findings do not suggest that routine staining for MUC2 will be useful to predict subsequent diagnosis of intestinal metaplasia in columnar lined oesophagus. References 1. McIntire M, Soucy G, Vaughan T, et al. MUC2 is a highly specific marker of goblet cell metaplasia in the distal oesophagus and the gastrooesophageal junction. Am J Surg Pathol 2011; 35: 1007–13. 2. Hahn H, Blount PL, Ayub K, et al. Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the oesophagus. Am J Surg Pathol 2009; 33: 1006– 15. 3. Chandrasoma P, Wijetunge S, DeMeester S, et al. Columnar-lined oesophagus without intestinal metaplasia has no proven risk of adenocarcinoma. Am J Surg Pathol 2012; 36: 1–7. 4. Niv Y, Fass R. The role of mucin in GERD and its complications. Nat Rev Gastroenterol Hepatol 2011; 9: 55–9.
‘GIVE THEM AN INCH. . .’: DABIGATRAN PRESCRIPTION IN VICTORIA Sueh-li Lim, Shaun Fleming, Ellen Maxwell Melbourne Pathology, Collingwood, Vic, Australia Background: Dabigatran is a direct thrombin inhibitor recently available through a physician familiarisation program (PFP) for prophylaxis of patients with non-valvular atrial fibrillation. The PFP was supported by pharmaceutical industry sponsored education. National and international reports of bleeding associated with this drug suggest inappropriate patient selection. Objectives: To compare the characteristics of local patients prescribed dabigatran for the prevention of stroke with the RE-LY study population. Methods: Retrospective analysis of patients exiting our oral anticoagulant service, transferred to dabigatran from warfarin, between June and November 2011 inclusive. Results: 362 patients were known to be prescribed dabigatran. They were on average older than those of the RE-LY study (median age 78 versus 71 years), included those with significant renal impairment eGFR <50 mL/min/1.73m2 (51/362, 14%) and patients in whom renal function (45/362, 12%) was not assessed. Two hundred and thirteen patients (58.8%) were transferred to dabigatran despite high quality anticoagulant management, defined as a time in therapeutic range (TTR) >65%; average TTR was 70% compared to 64% in the RE-LY study. Mild thrombocytopenia and concurrent antiplatelet drugs were noted in 12% and 15%, respectively. Conclusions: Our study confirms prescription of dabigatran to a local population dissimilar to the RE-LY cohort.
Pathology (2012), 44(S1)
IMP3 STAINING IS NOT A USEFUL MARKER FOR ADRENOCORTICAL CARCINOMA H. M. Manuchehri, A. Clarkson, L. Siosson, A. J. Gill Royal North Shore Hospital, Sydney, NSW, Australia Adrenocortical carcinoma (ACC) is a rare tumour with challenging pathological diagnosis. The Weiss scoring system which is based on the recognition of at least three of nine morphological parameters is the most widely used criteria. However the Weiss system is not entirely sensitive or specific, and some of the criteria are subjective and potentially problematic. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC. Alterations of the insulin-like growth factor-II (IGF-2) molecule seem to be promising particularly when used in conjunction with Ki67 index. The insulin-like growth factor-II mRNAbinding protein (IMP3) has been shown to be a useful marker of malignancy in multiple organs. We investigated IMP3 expression by immunohistochemistry in TMAs of 35 ACCs and 161 adrenal cortical adenomas. IMP3 immunoreactivity was seen in two (6%) ACC and in none of the adrenal cortical adenomas. We conclude that despite its high specificity for the diagnosis of malignancy in adrenal cortical neoplasms, its very low sensitivity means IMP3 overexpression is unlikely to be useful in the diagnostic setting. References 1. Findeis-Hosey JJ, H Xu H. The use of insulin like-growth factor II messenger RNA binding protein –3 in diagnostic pathology. Hum Pathol 2011; 42: 303– 14. 2. Volante M, Buttigliero C,Greco E, et al. Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 2008; 61: 787–93. 3. Soon PS, Gill AJ, Clarkson, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumours identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer 2009; 16: 573–83.
A REVIEW OF DIAGNOSTIC UTILITY OF P16INK4A IMMUNOSTAINING AS A MARKER OF HIGH-RISK HPV AND HIGH-GRADE CERVICAL INTRAEPITHELIAL NEOPLASIA Ali Moghimi, Simon Nazaretian Anatomical Pathology Department, The Royal Women’s Hospital, Parkville, Vic, Australia The most frequent type of cervical cancer is squamous-cell carcinoma which develops from cervical intraepithelial neoplasia (CIN) / squamous intraepithelial lesion (SIL). Its tumorigenesis is related to human papillomavirus (HPV). High-risk HPV is integrated into the genome and leads to tumour progression. Cytological screening leads to detection of precursors and their mimics. P16INK4a and Ki-67 immunohistochemistry assists in the histological differential diagnosis of precursors to reactive and metaplastic epithelium. P16INK4a has emerged as a valuable surrogate marker for high-risk HPV infection and shows increased immunoexpression with worsening grades of CIN. Numerous studies have supported its role in the detection of high-grade dysplasia and have lead to the use of p16INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16INK4a in everyday practice, including the problems in the interpretation of the patterns of immunostaining and standardisation of the p16INK4a scoring.
Copyright © Royal College of pathologists of Australasia. Unauthorized reproduction of this article is prohibited.