Value of PAX 8 immunostaining in tumor diagnosis: A review and update

Advances in Anatomic Pathology

Volumn 19, Issue 3, 2012, Pages 140-151

  Ordóñez, Nelson G ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

immunohistochemistry; PAX 8; transcription factor

Indexed keywords

THYROGLOBULIN; THYROID TRANSCRIPTION FACTOR 1; TRANSCRIPTION FACTOR PAX2; TRANSCRIPTION FACTOR PAX4; TRANSCRIPTION FACTOR PAX5; TRANSCRIPTION FACTOR PAX6; TRANSCRIPTION FACTOR PAX8;

ACINAR CELL CARCINOMA; ADENOSQUAMOUS CARCINOMA; ADRENAL CORTEX TUMOR; AMINO TERMINAL SEQUENCE; ANAPLASTIC CARCINOMA; APPENDIX CARCINOMA; B CELL LYMPHOMA; BLADDER CARCINOMA; BREAST ADENOCARCINOMA; CARCINOID; CLEAR CELL CARCINOMA; COLON ADENOCARCINOMA; CROSS REACTION; CYSTADENOMA; DIFFERENTIAL DIAGNOSIS; DUODENUM TUMOR; ENDOMETRIOID CARCINOMA; ENDOMETRIUM CARCINOMA; EPITHELIUM TUMOR; ESOPHAGEAL ADENOCARCINOMA; FEMALE GENITAL TRACT TUMOR; GENE DELETION; GENE EXPRESSION; HUMAN; ILEUM TUMOR; IMMUNOHISTOCHEMISTRY; KIDNEY CARCINOMA; KIDNEY TUMOR; LIVER CARCINOMA; LIVER CELL CARCINOMA; LUNG CARCINOMA; MIXED MULLERIAN TUMOR; MUCINOUS CARCINOMA; NEPHROBLASTOMA; NEUROENDOCRINE TUMOR; NONHUMAN; OVARY CARCINOMA; PANCREAS ADENOCARCINOMA; PANCREAS ISLET BETA CELL; PANCREAS ISLET DELTA CELL; PANCREAS TUMOR; PARATHYROID ADENOMA; PARATHYROID HYPERPLASIA; PARATHYROID TUMOR; PERITONEUM MESOTHELIOMA; POORLY DIFFERENTIATED THYROID CANCER; PRIORITY JOURNAL; PROSTATE ADENOCARCINOMA; RECTUM CARCINOMA; REVIEW; SKIN CARCINOMA; SMALL CELL CARCINOMA; SQUAMOUS CELL CARCINOMA; STOMACH ADENOCARCINOMA; STOMACH CARCINOMA; STOMACH TUMOR; THYMOMA; THYROID ADENOMA; THYROID FOLLICULAR CARCINOMA; THYROID MEDULLARY CARCINOMA; THYROID PAPILLARY CARCINOMA; THYROID TUMOR; TRANSITIONAL CELL CARCINOMA; TUMOR DIAGNOSIS; TUMOR DIFFERENTIATION; UTERINE CERVIX CARCINOMA;

ANIMALS; FEMALE; GENITAL NEOPLASMS, FEMALE; HUMANS; IMMUNOHISTOCHEMISTRY; KIDNEY; KIDNEY NEOPLASMS; NEUROENDOCRINE TUMORS; OVARIAN NEOPLASMS; PAIRED BOX TRANSCRIPTION FACTORS; PARATHYROID NEOPLASMS; THYMOMA; THYMUS NEOPLASMS; THYROID NEOPLASMS; TUMOR MARKERS, BIOLOGICAL; UTERINE CERVICAL NEOPLASMS;

EID: 84859940213     PISSN: 10724109     EISSN: 15334031     Source Type: Journal    
DOI: 10.1097/PAP.0b013e318253465d     Document Type: Review

References (80)

1. Gruss P, Walther C. Pax in development. Cell. 1992;69: 719-722.
2. Mansouri A, Hallonet M, Gruss P. Pax genes and their roles in cell differentiation and development. Curr Opin Cell Biol. 1996;8:851-857. (Pubitemid 26399946)
3. Dahl E, Koseki H, Balling R. Pax genes and organogenesis. Bioessays. 1997;19:755-765. (Pubitemid 27383751)
4. Lang D, Powell SK, Plummer RS, et al. PAX genes: roles in development, pathophysiology, and cancer. Biochem Pharmacol. 2007;73:1-14. (Pubitemid 44868976)
5. Bopp D, Burri M, Baumgartner S, et al. Conservation of a large protein domain in the segmentation gene paired and in functionally related genes of Drosophila. Cell. 1986;47:1033-1040. (Pubitemid 17005075)
6. Treisman J, Harris E, Desplan C. The paired box encodes a second DNA-binding domain in the paired homeo domain protein. Genes Dev. 1991;5:594-604. (Pubitemid 21905980)
7. Stoykova A, Gruss P. Roles of Pax genes in developing and adult brain as suggested by expression patterns. J Neurosci. 1994;14:1395-1412. (Pubitemid 24079992)
8. Mittag J, Winterhager E, Bauer K, et al. Congenital hypothyroid female pax8-deficient mice are infertile despite thyroid hormone replacement therapy. Endocrinology. 2007;148:719-725. (Pubitemid 46143173)
9. Bouchard M, de Caprona D, Busslinger M, et al. Pax2 and Pax8 cooperate in mouse inner ear morphogenesis and innervation. BMC Dev Biol. 2010;10:89.
10. Macchia PE, Lapi P, Krude H, et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet. 1998;19:83-86. (Pubitemid 28242030)
11. Vilain C, Rydlewski C, Duprez L, et al. Autosomal dominant transmission of congenital thyroid hypoplasia due to lossof- function mutation of PAX8. J Clin Endocrinol Metab. 2001;86:234-238. (Pubitemid 32109801)
12. Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet. 2005;42:379-389. (Pubitemid 40685678)
13. Pasca di Magliano M, Di Lauro R, Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc Natl Acad Sci USA. 2000;97:13144-13149.
14. Nonaka D, Tang Y, Chiriboga L, et al. Diagnostic utility of thyroid transcription factor Pax8 and TTF-2 (FOXE1) in thyroid epithelial neoplasms. Mod Pathol. 2008;21:192-200. (Pubitemid 351172171)
15. Puglisi F, Cesselli D, Damante G, et al. Expression of Pax-8, p53 and bcl-2 in human benign and malignant thyroid diseases. Anticancer Res. 2000;20:311-316. (Pubitemid 30189772)
16. Scouten WT, Patel A, Terrell R, et al. Cytoplasmic localization of the paired box gene, Pax-8, is found in pediatric thyroid cancer and may be associated with a greater risk of recurrence. Thyroid. 2004;14:1037-1046. (Pubitemid 40076128)
17. Zhang P, Zuo H, Nakamura Y, et al. Immunohistochemical analysis of thyroid-specific transcription factors in thyroid tumors. Pathol Int. 2006;56:240-245.
18. Laury AR, Perets R, Piao H, et al. A comprehensive analysis of PAX8 expression in human epithelial tumors. Am J Surg Pathol. 2011;35:816-826.
19. Tacha D, Zhou D, Cheng L. Expression of PAX8 in normal and neoplastic tissues: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol. 2011;19:293-299.
20. Rivera M, Sang C, Gerhard R, et al. Anaplastic thyroid carcinoma: morphologic findings and PAX-8 expression in cytology specimens. Acta Cytol. 2010;54:668-672.
21. Bishop JA, Sharma R, Westra WH. PAX8 immunostaining of anaplastic thyroid carcinoma: a reliable means of discerning thyroid origin for undifferentiated tumors of the head and neck. Hum Pathol. 2011;42:1873-1877.
22. Ordóñez NG, El-Naggar AK, Hickey RC, et al. Anaplastic thyroid carcinoma. Immunocytochemical study of 32 cases. Am J Clin Pathol. 1991;96:15-24.
23. Miettinen M, Franssila KO. Variable expression of keratins and nearly uniform lack of thyroid transcription factor 1 in thyroid anaplastic carcinoma. Hum Pathol. 2000;31:1139-1145.
24. Rosai J, Carcangiu ML. Pitfalls in the diagnosis of thyroid neoplasms. Pathol Res Pract. 1987;182:169-179. (Pubitemid 17059134)
25. Ozcan A, Shen SS, Hamilton C, et al. PAX 8 expression in non-neoplastic tissues, primary tumors, and metastatic tumors: a comprehensive immunohistochemical study. Mod Pathol. 2011;24:751-764.
26. Narlis M, Grote D, Gaitan Y, et al. Pax2 and pax8 regulate branching morphogenesis and nephron differentiation in the developing kidney. J Am Soc Nephrol. 2007;18:1121-1129. (Pubitemid 46536898)
27. Tong GX, Yu WM, Beaubier NT, et al. Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study. Mod Pathol. 2009;22:1218-1227.
28. Tong GX, Weeden EM, Hamele-Bena D, et al. Expression of PAX8 in nephrogenic adenoma and clear cell adenocarcinoma of the lower urinary tract: evidence of related histogenesis? Am J Surg Pathol. 2008;32:1380-1387.
29. Albadine R, Schultz L, Illei P, et al. PAX8 (+)/p63 ( ) immunostaining pattern in renal collecting duct carcinoma (CDC): a useful immunoprofile in the differential diagnosis of CDC versus urothelial carcinoma of upper urinary tract. Am J Surg Pathol. 2010;34:965-969.
30. Fujiwara M, Taube J, Sharma M, et al. PAX8 discriminates ovarian metastases from adnexal tumors and other cutaneous metastases. J Cutan Pathol. 2010;37:938-943.
31. Carney EM, Banerjee P, Ellis CL, et al. PAX2( )/PAX8( )/ inhibin A(+) immunoprofile in hemangioblastoma: a helpful combination in the differential diagnosis with metastatic clear cell renal cell carcinoma to the central nervous system. Am J Surg Pathol. 2011;35:262-267.
32. Sangoi AR, Fujiwara M, West RB, et al. Immunohistochemical distinction of primary adrenal cortical lesions from metastatic clear cell renal cell carcinoma: a study of 248 cases. Am J Surg Pathol. 2011;35:678-686.
33. Daniel L, Lechevallier E, Giorgi R, et al. Pax-2 expression in adult renal tumors. Hum Pathol. 2001;32:282-287. (Pubitemid 32246801)
34. Mazal PR, Stichenwirth M, Koller A, et al. Expression of aquaporins and PAX-2 compared to CD10 and cytokeratin 7 in renal neoplasms: a tissue microarray study. Mod Pathol. 2005;18:535-540. (Pubitemid 40478117)
35. Memeo L, Jhang J, Assaad AM, et al. Immunohistochemical analysis for cytokeratin 7, KIT, and PAX2: value in the differential diagnosis of chromophobe cell carcinoma. Am J Clin Pathol. 2007;127:225-229. (Pubitemid 46797179)
36. Wasco MJ, Pu RT. Comparison of PAX-2, RCC antigen, and antiphosphorylated H2AX antibody (gamma-H2AX) in diagnosing metastatic renal cell carcinoma by fine-needle aspiration. Diagn Cytopathol. 2008;36:568-573.
37. Gupta R, Balzer B, Picken M, et al. Diagnostic implications of transcription factor Pax 2 protein and transmembrane enzyme complex carbonic anhydrase IX immunoreactivity in adult renal epithelial neoplasms. Am J Surg Pathol. 2009;33: 241-247.
38. Ozcan A, Zhai J, Hamilton C, et al. PAX-2 in the diagnosis of primary renal tumors: immunohistochemical comparison with renal cell carcinoma marker antigen and kidney-specific cadherin. Am J Clin Pathol. 2009;131:393-404.
39. Zhai QJ, Ozcan A, Hamilton C, et al. PAX-2 expression in non-neoplastic, primary neoplastic, and metastatic neoplastic tissue: a comprehensive immunohistochemical study. Appl Immunohistochem Mol Morphol. 2010;18:323-332.
40. Gokden N, Gokden M, Phan DC, et al. The utility of PAX-2 in distinguishing metastatic clear cell renal cell carcinoma from its morphologic mimics: an immunohistochemical study with comparison to renal cell carcinoma marker. Am J Surg Pathol. 2008;32:1462-1467.
41. Ozcan A, Zhai Q, Javed R, et al. PAX-2 is a helpful marker for diagnosing metastatic renal cell carcinoma: comparison with the renal cell carcinoma marker antigen and kidney-specific cadherin. Arch Pathol Lab Med. 2010;134:1121-1129.
42. Leroy X, Farine MO, Buob D, et al. Diagnostic value of cytokeratin 7, CD10 and mesothelin in distinguishing ovarian clear cell carcinoma from metastasis of renal clear cell carcinoma. Histopathology. 2007;51:874-876. (Pubitemid 350179412)
43. Rivera AL, Takei H, Zhai J, et al. Useful immunohistochemical markers in differentiating hemangioblastoma versus metastatic renal cell carcinoma. Neuropathology. 2010;30:580-585.
44. McKenney JK, Fujiwara M, Higgins JP, et al. Comparison of putative renal cell carcinoma (RCC) immunohistochemical (IHC) markers in primary adrenal cortical lesions (ACL) and metastatic RCC: a tissue microarray study of 246 cases. Mod Pathol. 2009;22(suppl 1):182 A.
45. Genega EM, Ghebremichael M, Najarian R, et al. Carbonic anhydrase IX expression in renal neoplasms: correlation with tumor type and grade. Am J Clin Pathol. 2010;134: 873-879.
46. Sangoi AR, West RB, Bonventre JV, et al. Exploring the specificity of putative renal cell carcinoma (RCC) markers in non-renal tissues and neoplasms from various organ systems: a tissue microarray (TMA) study of 501 cases. Mod Pathol. 2010;23(suppl 1):216A.
47. Simsir A, Chhieng D, Wei XJ, et al. Utility of CD10 and RCCma in the diagnosis of metastatic conventional renal-cell adenocarcinoma by fine-needle aspiration biopsy. Diagn Cytopathol. 2005;33:3-7. (Pubitemid 40934413)
48. Butnor KJ, Nicholson AG, Allred DC, et al. Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma. Arch Pathol Lab Med. 2006;130:823-827. (Pubitemid 43887002)
49. Bakshi N, Kunju LP, Giordano T, et al. Expression of renal cell carcinoma antigen (RCC) in renal epithelial and nonrenal tumors: diagnostic implications. Appl Immunohistochem Mol Morphol. 2007;15:310-315. (Pubitemid 47329924)
50. Ingold B, Wild PJ, Nocito A, et al. Renal cell carcinoma marker reliably discriminates central nervous system haemangioblastoma from brain metastases of renal cell carcinoma. Histopathology. 2008;52:674-681. (Pubitemid 351600042)
51. Yoshida SO, Imam A. Monoclonal antibody to a proximal nephrogenic renal antigen: immunohistochemical analysis of formalin-fixed, paraffin-embedded human renal cell carcinomas. Cancer Res. 1989;49:1802-1809. (Pubitemid 19108408)
52. McGregor DK, Khurana KK, Cao C, et al. Diagnosing primary and metastatic renal cell carcinoma: the use of the monoclonal antibody "renal cell carcinoma marker". Am J Surg Pathol. 2001;25:1485-1492. (Pubitemid 33096962)
53. Cameron RI, Ashe P, O'Rourke DM, et al. A panel of immunohistochemical stains assists in the distinction between ovarian and renal clear cell carcinoma. Int J Gynecol Pathol. 2003;22:272-276. (Pubitemid 36750410)
54. Sharma SG, Gokden M, McKenney JK, et al. The utility of PAX-2 and renal cell carcinoma marker immunohistochemistry in distinguishing papillary renal cell carcinoma from nonrenal cell neoplasms with papillary features. Appl Immunohistochem Mol Morphol. 2010;18:494-498.
55. Yan M, Ghorab Z, Nadji M. Renal cell carcinoma antigen is expressed by yolk sac tumors and yolk sac elements of embryonal carcinomas. Appl Immunohistochem Mol Morphol. 2003;11:113-115. (Pubitemid 36749561)
56. Ordóñez NG. The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study. Hum Pathol. 2004;35: 697-710. (Pubitemid 38881080)
57. Bowen NJ, Logani S, Dickerson EB, et al. Emerging roles for PAX8 in ovarian cancer and endosalpingeal development. Gynecol Oncol. 2007;104:331-337. (Pubitemid 46135661)
58. Ozcan A, Liles N, Coffey D, et al. PAX2 and PAX8 expression in primary and metastatic Müllerian epithelial tumors: a comprehensive comparison. Am J Surg Pathol. 2011;35:1837-1847.
59. Köbel M, Kalloger SE, Boyd N, et al. Ovarian carcinoma subtypes are different diseases: implications for biomarker studies. PLoS Med. 2008;5:e232.
60. Nonaka D, Chiriboga L, Soslow RA. Expression of pax8 as a useful marker in distinguishing ovarian carcinomas from mammary carcinomas. Am J Surg Pathol. 2008;32: 1566-1571.
61. Lotan TL, Ye H, Melamed J, et al. Immunohistochemical panel to identify the primary site of invasive micropapillary carcinoma. Am J Surg Pathol. 2009;33:1037-1041.
62. Tong GX, Devaraj K, Hamele-Bena D, et al. Pax8: a marker for carcinoma of Müllerian origin in serous effusions. Diagn Cytopathol. 2011;39:567-574.
63. Tabrizi AD, Kalloger SE, Köbel M, et al. Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases. Int J Gynecol Pathol. 2010;29:99-107.
64. Chu PG, Chung L, Weiss LM, et al. Determining the site of origin of mucinous adenocarcinoma: an immunohistochemical study of 175 cases. Am J Surg Pathol. 2011;35:1830-1836.
65. Zhao L, Guo M, Sneige N, et al. Value of PAX8 and WT1 immunostaining in confirming the ovarian origin of metastatic carcinoma in serous effusion specimens. Am J Clin Pathol. 2012;137:304-309.
66. Brunner AH, Riss P, Heinze G, et al. Immunoexpression of PAX 8 in endometrial cancer: relation to high-grade carcinoma and p53. Int J Gynecol Pathol. 2011;30:569-575.
67. Sosa-Pineda B. The gene Pax4 is an essential regulator of pancreatic beta-cell development. Mol Cells. 2004;18:289-294. (Pubitemid 40298022)
68. St-Onge L, Sosa-Pineda B, Chowdhury K, et al. Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. Nature. 1997;387:406-409. (Pubitemid 27227205)
69. Long KB, Srivastava A, Hirsch MS, et al. PAX8 expression in well-differentiated pancreatic endocrine tumors: correlation with clinicopathologic features and comparison with gastrointestinal and pulmonary carcinoid tumors. Am J Surg Pathol. 2010;34:723-729.
70. Haynes CM, Sangoi AR, Pai RK. PAX8 is expressed in pancreatic well-differentiated neuroendocrine tumors and in extrapancreatic poorly differentiated neuroendocrine carcinomas in fine-needle aspiration biopsy specimens. Cancer Cytopathol. 2011;119:193-201.
71. Sangoi AR, Ohgami RS, Pai RK, et al. PAX8 expression reliably distinguishes pancreatic well-differentiated neuroendocrine tumors from ileal and pulmonary well-differentiated neuroendocrine tumors and pancreatic acinar cell carcinoma. Mod Pathol. 2011;24:412-424.
72. Lorenzo PI, Jimenez Moreno CM, Delgado I, et al. Immunohistochemical assessment of Pax8 expression during pancreatic islet development and in human neuroendocrine tumors. Histochem Cell Biol. 2011;136:595-607.
73. Pellizzari L, Puppin C, Mariuzzi L, et al. PAX8 expression in human bladder cancer. Oncol Rep. 2006;16:1015-1020.
74. Weissferdt A, Moran CA. Pax8 expression in thymic epithelial neoplasms: an immunohistochemical analysis. Am J Surg Pathol. 2011;35:1305-1310.
75. Laury AR, Hornick JL, Perets R, et al. PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma. Am J Surg Pathol. 2010;34:627-635.
76. Moretti L, Medeiros LJ, Kunkalla K, et al. N-terminal PAX8 polyclonal antibody shows cross-reactivity with N-terminal region of PAX5 and is responsible for reports of PAX8 positivity in malignant lymphomas. Mod Pathol. 2012;25:231-236.
77. Ordóñez NG. What are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update. Hum Pathol. 2007;38:1-16. (Pubitemid 44880219)
78. Al-Hussaini M, Stockman A, Foster H, et al. WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology. 2004;44:109-115. (Pubitemid 38296970)
79. Ordóñez NG. Value of estrogen and progesterone receptor immunostaining in distinguishing between peritoneal mesotheliomas and serous carcinomas. Hum Pathol. 2005;36:1163-1167. (Pubitemid 41541966)
80. Ordóñez NG. The diagnostic utility of immunohistochemistry and electron microscopy in distinguishing between peritoneal mesotheliomas and serous carcinomas: a comparative study. Mod Pathol. 2006;19:34-48. (Pubitemid 43250977)