PAX8 – Antibody Lexicon

by Jan Klos

Background

PAX genes are the family of cell-lineage related transcription factors that play fundamental roles during organogenesis. The protein encoded by PAX8 gene ((chr 2 2q14.1) is mainly expressed in embryonic tissues. In adults it is found i normal and neoplastic tissues of thyroid gland, kidney and organs of Müllerian system.

Staining pattern

Nuclear.

Expression in normal tissues

Cells of kidney tubules and parietal cells in Bowmans capsule, urothelium, Langerhans’s islands in pancreas, thyroid gland, Fallopian tube, endometrial epithelium are positive. All other normal tissues including ovary are negative. Several antibodies raised against the N-terminal part of PAX8 molecule (all tested polyclonal as well as clones mAb clones MRQ-50, C12A32, IHC008, H5A8, PAX8R1 and rmAb 2774R) show cross reactivity with other members of PAX family especially PAX5 and stained also B-lymphocytes. Some of the clones may also show different spectrum of reactivity. The rmAb clones EP298, SP348 and ZR-1 directed against the C terminus did not show this cross-reactivity (according to NordiQC Run 64, 60 and 56).

Expression in tumors

Almost all cases (>90%) of serous and clear cell carcinoma of the ovary, renal tumors (clear cell, medullary, collecting duct, papillary renal cell carcinoma and renal oncocytoma), papillary and follicular thyroid carcinoma, adenocarcinoma in situ and HSIL in uterine cervix, clear cell carcinoma of urinary bladder, cystic and papillary of peritoneal mesothelioma, parathyroid adenoma are positive. Majority (50-90%) of cases of endometrioid carcinoma of the ovary and uterine corpus, chromophobe and translocation renal cell carcinoma, anaplastic and medullary thyroid carcinoma, adenocarcinoma of uterine cervix, carcinoid of duodenum and colon, neuroendocrine tumors of the pancreas and Merkel cell carcinoma are also positive. Positivity is also reported in minority of cases (10-50%) of primary ovarian mucinous carcinoma, squamous cell carcinoma of uterine cervix, carcinoid of ventricle, appendix and rectum, ductal adenocarcinoma of the pancreas, urothelial carcinoma and malignant peritoneal mesothelioma. Fewer than 10% of cases of carcinoid in ileum and bronchus as well as pleural mesothelioma are reported positive. Ductal and lobular breast carcinoma, lung adenocarcinoma, majority of squamous cell carcinoma, adenocarcinoma of gastrointestinal tract, adenocarcinoma of prostate, hepatocellular carcinoma, head and neck carcinomas, and adrenocortical tumors are considered negative. Most of the cases of small cell carcinoma are considered negatiove but variation related to applied clone is reported,
Polyclonal antibodies stain positive thymomas, seminomas and some B-cell lymphomas (due to cross-reactivity with other members of PAX family) but staining with monoclonal antibodies are negative.
Monoclonal antibodies do not stain normal parathyroid tissue. Polyclonal antibodies stain positive only minority of normal parathyroid glands, but stain positive majority of parathyroid adenoma and hyperplasia.

Control tissue

Kidney or Fallopian tube.

Application

Recommended in panel when ovarian, renal, Müllerian and thyroid are considered e.g. malignant mesothelioma (negative) vs. serous carcinoma (positive) or breast carcinoma (negative) vs. serous carcinoma (positive) etc.
Single cases of squamous cell carcinoma of the lung, uterine cervix as well as varying number of other tumors including pancreas adenocarcinoma, cholangiocarcinoma, neuroendocrine tumors and even GIST are reported positive.
Positive staining of B-lymphoid cells with some antibodies (see above) may be confusing.
Interpretation should be careful since there might be a number of unreported/unknown positive cases among other tumors and use of properly designed antibody panel is mandatory.
Variation in the performance of different clones should be carefuly considered when selecting the clone for diagnostic use

by Jan Klos

Background

Staining pattern

Expression in normal tissues

Expression in tumors

Control tissue

Application

Selected references