Study of Serum PSA, AMACR, P63 And PTEN in Prostatic Adenocarcinoma
Keywords:
Prostatic adenocarcinoma, immunohistochemistry, P63, AMACR, PTEN
Abstract
Background: Prostatic adenocarcinoma is the most common malignancy in older males. The present study was planned with an aim to evaluate serum PSA, expression of P63, AMACR and PTEN in prostatic carcinoma and to correlate them clinico-pathologically. It is a descriptive analytical study which includes patients of prostatic adenocarcinoma reporting to a large tertiary care hospital in Lucknow during the period of 2015-to 2017. Methods: Clinical details and complete hematological workup was done in 50 cases of prostatic adenocarcinoma during our study period of two years. Routine histopathology with hematoxylin and eosin (H & E) staining was done. Gleason grading was performed. Relevant sections were taken for Immunohistochemistry (IHC) to study PTEN, AMACR and P63. Result: Serum PSA levels ranged from 7.5 to 60 ng/ml. Half the patients had S. PSA in range 10-20 ng/ml (50%) followed by <10 ng/ml (32%) and >20 ng/ml (18%) respectively. Mean S. PSA levels were 17.25+14.01 ng/ml. p63 assessment was conclusive in 48 cases. Expression of p63 was seen in 20 (41.7%) cases only (Score 1 or above). Maximum number of cases showing p63 expression had score 1 (35.4%) followed by score 2 (n=2; 4.2%) and score 3 (2.1%) respectively. AMACR assessment was conclusive in 48 cases. Expression of AMACR was seen in 47/48 (97.9%) cases. Maximum had score 2+ (n=22; 45.8%) followed by Score 3+ (n=18; 37.5%), score 1+ (n=7; 14.6%) and score 0 (n=1; 2.1%) respectively. PTEN assessment was conclusive in 46 cases. There were 21 (45.7%) cases with score 0, 16 (34.8%) with score 1 and 9 (19.6%) with score 2. Conclusion: In present study, serum PSA levels of patients ranged from 7.5 to 60 ng/ml with half having S. PSA in 10-20 ng/ml range (50%). According to AJCC criteria, S. PSA levels <10 ng/ml are in general indicators of lower severity of prostate cancer while those in 10-20 ng/ml range indicate an intermediate severity of prostate cancer.References
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015; 136: E359-E386.
2 Lalitha K, Suman G, Pruthvish S, Mathew A, Murthy NS. Estimation of time trends of incidence of prostate cancer--an Indian scenario. Asian Pac J Cancer Prev. 2012;13(12):6245-50.
3 Balasubramaniam G, Talote S, Mahantshetty U, Saoba S, Shrivastava S. Prostate Cancer: A Hospital-Based Survival Study from Mumbai, India. Asian Pacific J Cancer Prev 2013; 14 (4): 2595-2598.
4 Yeole BB. Trends in the Prostate Cancer Incidence in India. Asian Pacific J Cancer Prev 2008; 9: 141-144.
5 National Cancer Institute of Canada (NCIC). Canadian Cancer Statistics 2013. Toronto, Canada: 2013.
6 Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66: 7-30.
7 Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006; 79: 85-94.
8 Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015; 136: E359-E386.
9 National Cancer Institute of Canada (NCIC). Canadian Cancer Statistics 2013. Toronto, Canada: 2013.
10 Lalitha K, Suman G, Pruthvish S, Mathew A, Murthy NS. Estimation of time trends of incidence of prostate cancer--an Indian scenario. Asian Pac J Cancer Prev. 2012;13(12):6245-50.
11 Balasubramaniam G, Talote S, Mahantshetty U, Saoba S, Shrivastava S. Prostate Cancer: A Hospital-Based Survival Study from Mumbai, India. Asian Pacific J Cancer Prev 2013; 14 (4): 2595-2598.
12 Yeole BB. Trends in the Prostate Cancer Incidence in India. Asian Pacific J Cancer Prev 2008; 9: 141-144.
3 Myrtle J, Ivor L. Measurement of PSA in Serum by two immunometric Methods (Hybritech Tandem-R/Tandem-E PSA). In: Catalona WJ, editor. Clinical Aspects of Prostate Cancer. New York: Elsevier; 1989. pp. 161–71.
4 Agnihotri S, Mittal RD, Kapoor R, Mandhani A. Raising cut-off value of prostate specific antigen (PSA) for biopsy in symptomatic men in India to reduce unnecessary biopsy. The Indian Journal of Medical Research. 2014;139(6):851-856.
5 Senior K. Age-specific PSA screening better. Lancet Oncol. 2007;8:378
16 Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA, et al. Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. JAMA. 1993;270:860–4.
17 Malati T, Kumari GR. Racial and ethnic variation of PSA in global population: Age specific reference intervals for serum prostate specific antigen in healthy South Indian males. Indian J Clin Biochem. 2004;19:132–7.
8 National Collaborating Centre for Cancer (UK). Prostate Cancer: Diagnosis and Treatment. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2014 Jan. (NICE Clinical Guidelines, No. 175.) 3, Diagnosis and staging of prostate cancer.
19 Shtricker A, Shefi S, Ringel A, Gilson G. PSA levels of 4.0 – 10 ng/ml and negative digital rectal examination. antibiotic therapy versus immediate prostate biopsy. Int Braz J Urol. 2009; 35: 551-8.
20 Wright JL, Lange PH. Newer Potential Biomarkers in Prostate Cancer. Reviews in Urology. 2007;9(4):207-213.
2 Jakobsen NA, Hamdy FC, Bryant RJ. Novel biomarkers for the detection of prostate cancer. Journal of Clinical Urology. 2016;9(2 Suppl):3-10.
22 Grisanzio C, Signoretti S 2008. p63 in prostate biology and pathology. J Cell Biochem103: 1354–1368.
23 Jiang Z, Li C, Fischer A, Dresser K, Woda BA 2005. Using an AMACR (P504S)/34βE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens. Am J Clin Pathol 123: 231–236 .
24 Phin S, Moore MW, Cotter PD. Genomic Rearrangements of PTEN in Prostate Cancer. Frontiers in Oncology. 2013;3:240.
25 Lotan TL, Gurel B, Sutcliffe S, et al. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients. Clinical Cancer Research. 2011;17(20):6563-6573.
26 Cuzick J., Yang Z.H., Fisher G. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer. 2013;108:2582–2589.
27 Schmitz M., Grignard G., Margue C. Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis. Int J Cancer. 2007;120:1284–1292.
28 Carver B.S., Chapinski C., Wongvipat J. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19:575–586.
29 Yoshimoto M., Cunha I.W., Coudry R.A. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer. 2007;97:678–685.
30 Reid A.H., Attard G., Ambroisine L. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer. 2010;102:678–684.
31 Leinonen K.A., Saramaki O.R., Furusato B. Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. Cancer Epidemiol Biomarkers Prev. 2013;22:2333–2344.
33 McMenamin M.E., Soung P., Perera S., Kaplan I., Loda M., Sellers W.R. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 1999;59:4291–4296.
34 Ma Q., Fu W., Li P. FoxO1 mediates PTEN suppression of androgen receptor N- and C-terminal interactions and coactivator recruitment. Mol Endocrinol. 2009;23:213–225.
35 Xu J, Stolk JA, Zhang X, et al. Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer Res. 2000;60:1677–1682.
36 Jiang Z, Woda BA, Rock KL, et al. P504S: a new molecular marker for the detection of prostate carcinoma.Am J Surg Pathol. 2001;25:1397–1404.
37 Luo J, Zha S, Gage WR, et al. Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer.Cancer Res. 2002;62:2220–2226.
38 Molinie V, Fromont G, Sibony M, et al. Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate. Mod Pathol. 2004;17:1180–1190.
39 Trpkov K, Bartczak-McKay J, Yilmaz A. Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens. Am J Clin Pathol.2009;132:211–220.
40 Herawi M, Epstein JI. Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason pattern 4 cribriform and noncribriform acinar adenocarcinomas of the prostate. Am J Surg Pathol. 2007;31:889–894.
41 Wang W, Sun X, Epstein JI. Partial atrophy on prostate needle biopsy cores: a morphologic and immunohistochemical study. Am J Surg Pathol. 2008; 32: 851–857.
42 Jiang Z, Fanger GR, Woda BA, et al. Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases. Hum Pathol. 2003;34:792–796.
43 Shilo K, Dracheva T, Mani H, et al. Alpha-methylacyl CoA racemase in pulmonary adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors: expression and survival analysis. Arch Pathol Lab Med. 2007; 131: 1555–1560.
44 Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S: Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat Med 1998, 4:839-843.
45 Senoo M, Seki N, Ohira M, Sugano S, Watanabe M, Inuzuka S, Okamoto T, Tachibana M, Tanaka T, Shinkai Y, Kato H: A second p53-related protein, p73L, with high homology to p73. Biochem Biophys Res Commun 1998, 248:603-607.
46 Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidransky D: A new human p53 homologue. Nat Med 1998,4:747-748 .
47 Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F: p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 1998, 2:305-316.
48 Lotan TL, Gurel B, Sutcliffe S, et al. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients. Clinical Cancer Research. 2011;17(20):6563-6573
49 Snedecor GW, Cochran WG. Statistical Methods. 8th Ed. Ames: Iowa State Press, 1989.
50 Weinstein MH, Signoretti S, Loda M. Diagnostic Utility of Immunohistochemical Staining for p63, a Sensitive Marker of Prostatic Basal Cells. Mod Pathol 2002;15(12):1302–1308.
51 Parsons JK, Gage WR, Nelson WG, De Marzo AM. p63 protein expression is rare in prostate adenocarcinoma: implications for cancer diagnosis and carcinogenesis. Urology. 2001 Oct;58(4):619-24.
52 Wu HH, Lapkus O, Corbin M. Comparison of 34betaE12 and P63 in 100 consecutive prostate carcinoma diagnosed by needle biopsies. Appl Immunohistochem Mol Morphol. 2004 Dec;12(4):285-9
53 Ananthanarayanan V, Deaton RJ, Yang XJ, Pins MR, Gann PH. Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer. Prostate. 2005 Jun 1;63(4):341-6.
54 Kaić G, Tomasović-Loncarić C. Alpha-methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesions. Diagn Cytopathol. 2009 Nov;37(11):803-8
55 Ozgur T, Atik E, Hakverdi S, Yaldiz M. The expressions of AMACR and iNOS in prostate adenocarcinomas. Pakistan Journal of Medical Sciences. 2013;29(2):610-613.
56 Box A, Alshalalfa M, Hegazy SA, Donnelly B, Bismar T. High alpha-methylacyl-CoA racemase (AMACR) is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer. Tumour Biol. 2016 Sep;37(9):12287-12299.
57 McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR. Loss of PTEN Expression in Paraffin-embedded Primary Prostate Cancer Correlates with High Gleason Score and Advanced Stage. Cancer Reseaarch 1999; 59(17): 4291-4297.
58 Kim SH, Kim SH, Joung JY, et al. Overexpression of ERG and Wild-Type PTEN Are Associated with Favorable Clinical Prognosis and Low Biochemical Recurrence in Prostate Cancer. Medeiros R, ed. PLoS ONE. 2015;10(4):e0122498.
59 Lotan TL, Wei W, Morais CL, Hawley ST, Fazli L,Hurtado-Coll A, et al. PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer. Eur. Urology 2016; 2: 180-188
60 McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR. Loss of PTEN Expression in Paraffin-embedded Primary Prostate Cancer Correlates with High Gleason Score and Advanced Stage. Cancer Reseaarch 1999; 59(17): 4291-4297.
61 Park SJ, Sung WJ, Kim MJ. p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors. The Korean Journal of Pathology 2010; 44: 597-604.
2 Lalitha K, Suman G, Pruthvish S, Mathew A, Murthy NS. Estimation of time trends of incidence of prostate cancer--an Indian scenario. Asian Pac J Cancer Prev. 2012;13(12):6245-50.
3 Balasubramaniam G, Talote S, Mahantshetty U, Saoba S, Shrivastava S. Prostate Cancer: A Hospital-Based Survival Study from Mumbai, India. Asian Pacific J Cancer Prev 2013; 14 (4): 2595-2598.
4 Yeole BB. Trends in the Prostate Cancer Incidence in India. Asian Pacific J Cancer Prev 2008; 9: 141-144.
5 National Cancer Institute of Canada (NCIC). Canadian Cancer Statistics 2013. Toronto, Canada: 2013.
6 Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2016. CA Cancer J Clin 2016; 66: 7-30.
7 Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006; 79: 85-94.
8 Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015; 136: E359-E386.
9 National Cancer Institute of Canada (NCIC). Canadian Cancer Statistics 2013. Toronto, Canada: 2013.
10 Lalitha K, Suman G, Pruthvish S, Mathew A, Murthy NS. Estimation of time trends of incidence of prostate cancer--an Indian scenario. Asian Pac J Cancer Prev. 2012;13(12):6245-50.
11 Balasubramaniam G, Talote S, Mahantshetty U, Saoba S, Shrivastava S. Prostate Cancer: A Hospital-Based Survival Study from Mumbai, India. Asian Pacific J Cancer Prev 2013; 14 (4): 2595-2598.
12 Yeole BB. Trends in the Prostate Cancer Incidence in India. Asian Pacific J Cancer Prev 2008; 9: 141-144.
3 Myrtle J, Ivor L. Measurement of PSA in Serum by two immunometric Methods (Hybritech Tandem-R/Tandem-E PSA). In: Catalona WJ, editor. Clinical Aspects of Prostate Cancer. New York: Elsevier; 1989. pp. 161–71.
4 Agnihotri S, Mittal RD, Kapoor R, Mandhani A. Raising cut-off value of prostate specific antigen (PSA) for biopsy in symptomatic men in India to reduce unnecessary biopsy. The Indian Journal of Medical Research. 2014;139(6):851-856.
5 Senior K. Age-specific PSA screening better. Lancet Oncol. 2007;8:378
16 Oesterling JE, Jacobsen SJ, Chute CG, Guess HA, Girman CJ, Panser LA, et al. Serum prostate-specific antigen in a community-based population of healthy men: establishment of age-specific reference ranges. JAMA. 1993;270:860–4.
17 Malati T, Kumari GR. Racial and ethnic variation of PSA in global population: Age specific reference intervals for serum prostate specific antigen in healthy South Indian males. Indian J Clin Biochem. 2004;19:132–7.
8 National Collaborating Centre for Cancer (UK). Prostate Cancer: Diagnosis and Treatment. Cardiff (UK): National Collaborating Centre for Cancer (UK); 2014 Jan. (NICE Clinical Guidelines, No. 175.) 3, Diagnosis and staging of prostate cancer.
19 Shtricker A, Shefi S, Ringel A, Gilson G. PSA levels of 4.0 – 10 ng/ml and negative digital rectal examination. antibiotic therapy versus immediate prostate biopsy. Int Braz J Urol. 2009; 35: 551-8.
20 Wright JL, Lange PH. Newer Potential Biomarkers in Prostate Cancer. Reviews in Urology. 2007;9(4):207-213.
2 Jakobsen NA, Hamdy FC, Bryant RJ. Novel biomarkers for the detection of prostate cancer. Journal of Clinical Urology. 2016;9(2 Suppl):3-10.
22 Grisanzio C, Signoretti S 2008. p63 in prostate biology and pathology. J Cell Biochem103: 1354–1368.
23 Jiang Z, Li C, Fischer A, Dresser K, Woda BA 2005. Using an AMACR (P504S)/34βE12/p63 cocktail for the detection of small focal prostate carcinoma in needle biopsy specimens. Am J Clin Pathol 123: 231–236 .
24 Phin S, Moore MW, Cotter PD. Genomic Rearrangements of PTEN in Prostate Cancer. Frontiers in Oncology. 2013;3:240.
25 Lotan TL, Gurel B, Sutcliffe S, et al. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients. Clinical Cancer Research. 2011;17(20):6563-6573.
26 Cuzick J., Yang Z.H., Fisher G. Prognostic value of PTEN loss in men with conservatively managed localised prostate cancer. Br J Cancer. 2013;108:2582–2589.
27 Schmitz M., Grignard G., Margue C. Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis. Int J Cancer. 2007;120:1284–1292.
28 Carver B.S., Chapinski C., Wongvipat J. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19:575–586.
29 Yoshimoto M., Cunha I.W., Coudry R.A. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer. 2007;97:678–685.
30 Reid A.H., Attard G., Ambroisine L. Molecular characterisation of ERG, ETV1 and PTEN gene loci identifies patients at low and high risk of death from prostate cancer. Br J Cancer. 2010;102:678–684.
31 Leinonen K.A., Saramaki O.R., Furusato B. Loss of PTEN is associated with aggressive behavior in ERG-positive prostate cancer. Cancer Epidemiol Biomarkers Prev. 2013;22:2333–2344.
33 McMenamin M.E., Soung P., Perera S., Kaplan I., Loda M., Sellers W.R. Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage. Cancer Res. 1999;59:4291–4296.
34 Ma Q., Fu W., Li P. FoxO1 mediates PTEN suppression of androgen receptor N- and C-terminal interactions and coactivator recruitment. Mol Endocrinol. 2009;23:213–225.
35 Xu J, Stolk JA, Zhang X, et al. Identification of differentially expressed genes in human prostate cancer using subtraction and microarray. Cancer Res. 2000;60:1677–1682.
36 Jiang Z, Woda BA, Rock KL, et al. P504S: a new molecular marker for the detection of prostate carcinoma.Am J Surg Pathol. 2001;25:1397–1404.
37 Luo J, Zha S, Gage WR, et al. Alpha-methylacyl-CoA racemase: a new molecular marker for prostate cancer.Cancer Res. 2002;62:2220–2226.
38 Molinie V, Fromont G, Sibony M, et al. Diagnostic utility of a p63/alpha-methyl-CoA-racemase (p504s) cocktail in atypical foci in the prostate. Mod Pathol. 2004;17:1180–1190.
39 Trpkov K, Bartczak-McKay J, Yilmaz A. Usefulness of cytokeratin 5/6 and AMACR applied as double sequential immunostains for diagnostic assessment of problematic prostate specimens. Am J Clin Pathol.2009;132:211–220.
40 Herawi M, Epstein JI. Immunohistochemical antibody cocktail staining (p63/HMWCK/AMACR) of ductal adenocarcinoma and Gleason pattern 4 cribriform and noncribriform acinar adenocarcinomas of the prostate. Am J Surg Pathol. 2007;31:889–894.
41 Wang W, Sun X, Epstein JI. Partial atrophy on prostate needle biopsy cores: a morphologic and immunohistochemical study. Am J Surg Pathol. 2008; 32: 851–857.
42 Jiang Z, Fanger GR, Woda BA, et al. Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases. Hum Pathol. 2003;34:792–796.
43 Shilo K, Dracheva T, Mani H, et al. Alpha-methylacyl CoA racemase in pulmonary adenocarcinoma, squamous cell carcinoma, and neuroendocrine tumors: expression and survival analysis. Arch Pathol Lab Med. 2007; 131: 1555–1560.
44 Osada M, Ohba M, Kawahara C, Ishioka C, Kanamaru R, Katoh I, Ikawa Y, Nimura Y, Nakagawara A, Obinata M, Ikawa S: Cloning and functional analysis of human p51, which structurally and functionally resembles p53. Nat Med 1998, 4:839-843.
45 Senoo M, Seki N, Ohira M, Sugano S, Watanabe M, Inuzuka S, Okamoto T, Tachibana M, Tanaka T, Shinkai Y, Kato H: A second p53-related protein, p73L, with high homology to p73. Biochem Biophys Res Commun 1998, 248:603-607.
46 Trink B, Okami K, Wu L, Sriuranpong V, Jen J, Sidransky D: A new human p53 homologue. Nat Med 1998,4:747-748 .
47 Yang A, Kaghad M, Wang Y, Gillett E, Fleming MD, Dotsch V, Andrews NC, Caput D, McKeon F: p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell 1998, 2:305-316.
48 Lotan TL, Gurel B, Sutcliffe S, et al. PTEN Protein Loss by Immunostaining: Analytic Validation and Prognostic Indicator for a High Risk Surgical Cohort of Prostate Cancer Patients. Clinical Cancer Research. 2011;17(20):6563-6573
49 Snedecor GW, Cochran WG. Statistical Methods. 8th Ed. Ames: Iowa State Press, 1989.
50 Weinstein MH, Signoretti S, Loda M. Diagnostic Utility of Immunohistochemical Staining for p63, a Sensitive Marker of Prostatic Basal Cells. Mod Pathol 2002;15(12):1302–1308.
51 Parsons JK, Gage WR, Nelson WG, De Marzo AM. p63 protein expression is rare in prostate adenocarcinoma: implications for cancer diagnosis and carcinogenesis. Urology. 2001 Oct;58(4):619-24.
52 Wu HH, Lapkus O, Corbin M. Comparison of 34betaE12 and P63 in 100 consecutive prostate carcinoma diagnosed by needle biopsies. Appl Immunohistochem Mol Morphol. 2004 Dec;12(4):285-9
53 Ananthanarayanan V, Deaton RJ, Yang XJ, Pins MR, Gann PH. Alpha-methylacyl-CoA racemase (AMACR) expression in normal prostatic glands and high-grade prostatic intraepithelial neoplasia (HGPIN): association with diagnosis of prostate cancer. Prostate. 2005 Jun 1;63(4):341-6.
54 Kaić G, Tomasović-Loncarić C. Alpha-methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesions. Diagn Cytopathol. 2009 Nov;37(11):803-8
55 Ozgur T, Atik E, Hakverdi S, Yaldiz M. The expressions of AMACR and iNOS in prostate adenocarcinomas. Pakistan Journal of Medical Sciences. 2013;29(2):610-613.
56 Box A, Alshalalfa M, Hegazy SA, Donnelly B, Bismar T. High alpha-methylacyl-CoA racemase (AMACR) is associated with ERG expression and with adverse clinical outcome in patients with localized prostate cancer. Tumour Biol. 2016 Sep;37(9):12287-12299.
57 McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR. Loss of PTEN Expression in Paraffin-embedded Primary Prostate Cancer Correlates with High Gleason Score and Advanced Stage. Cancer Reseaarch 1999; 59(17): 4291-4297.
58 Kim SH, Kim SH, Joung JY, et al. Overexpression of ERG and Wild-Type PTEN Are Associated with Favorable Clinical Prognosis and Low Biochemical Recurrence in Prostate Cancer. Medeiros R, ed. PLoS ONE. 2015;10(4):e0122498.
59 Lotan TL, Wei W, Morais CL, Hawley ST, Fazli L,Hurtado-Coll A, et al. PTEN Loss as Determined by Clinical-grade Immunohistochemistry Assay Is Associated with Worse Recurrence-free Survival in Prostate Cancer. Eur. Urology 2016; 2: 180-188
60 McMenamin ME, Soung P, Perera S, Kaplan I, Loda M, Sellers WR. Loss of PTEN Expression in Paraffin-embedded Primary Prostate Cancer Correlates with High Gleason Score and Advanced Stage. Cancer Reseaarch 1999; 59(17): 4291-4297.
61 Park SJ, Sung WJ, Kim MJ. p16INK4a, PTEN, E-cadherin, Bcl-2 and Ki-67 Expression in Prostate Cancer: Its Relationship with the Metastatic Potential and Known Prognostic Factors. The Korean Journal of Pathology 2010; 44: 597-604.
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2019-11-19
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