Expression of galectin-3, nm-23, and cyclooxygenase-2 could potentially discriminate between benign and malignant pheochromocytoma.

Currently, the only reliable indicator of malignancy in pheochromocytoma is the presence of distant metastasis or extensive local invasion; predicting behavior of pheochromocytoma remains challenging. We aimed to correlate the behavior of pheochromocytoma with its expression of nm-23, cyclooxygenase (COX)-2, and galectin-3 (genes used to predict the course of some neoplastic diseases), evaluated immunohistochemically in 55 paraffin blocks of formalin-fixed pheochromocytoma specimens with confirmed behavior. In 3 (7%) of 44 benign and 7 (64%) of 11 malignant pheochromocytomas, there was negative nm-23 expression (P = .000). COX-2 immunoreactivity was positive in 10 (23%) of benign and 9 (82%) of malignant tumors (P = .000). Galectin-3 was expressed in 5 (11%) of benign and 9 (82%) of malignant pheochromocytomas (P = .000). Negative nm-23, along with positive COX-2 or galectin-3, predicted malignancy with 100% specificity. Dual negativity for galectin-3 and COX-2, along with nm-23 positivity, indicated benign behavior with 100% sensitivity. In early pheochromocytoma, evaluation of nm-23, galectin-3, and COX-2 expression could predict the outcome. Larger studies seem necessary to confirm the potential practical value of our findings.

[1]  C. Fletcher,et al.  Diagnostic histopathology of tumors , 2013 .

[2]  S. Silverberg,et al.  Silverberg's principles and practice of surgical pathology and cytopathology vol. 1 , 2013 .

[3]  D. E. Mills,et al.  Sternberg's Diagnostic Surgical Pathology , 2012 .

[4]  R. Heshmat,et al.  Immunohistochemical expression of Ki67, c-erbB-2, and c-kit antigens in benign and malignant pheochromocytoma. , 2010, Pathology, research and practice.

[5]  A. Mansoor Modern Surgical Pathology , 2010 .

[6]  Xiang Li,et al.  [The effects of nm23-H1 gene cell transfection on abilities of invasion, adhesion and chemotherapeutic sensitivity of bladder cancer T-24 cell line]. , 2007, Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition.

[7]  M. Chou,et al.  Prognostic significance of expression of nm23-H1 and focal adhesion kinase in non-small cell lung cancer. , 2007, Oncology reports.

[8]  A. Popovtzer,et al.  Cyclooxygenase‐2 expression in medullary thyroid carcinoma , 2007, Head & neck.

[9]  G. Kayser,et al.  The role of microvascularization and growth/adhesion-regulatory lectins in the prognosis of non-small cell lung cancer in stage II. , 2007, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[10]  L. Habel,et al.  NSAIDs and breast cancer recurrence in a prospective cohort study , 2007, Cancer Causes & Control.

[11]  J. Ochieng,et al.  Mechano-transduction mediated secretion and uptake of galectin-3 in breast carcinoma cells: implications in the extracellular functions of the lectin. , 2007, Experimental cell research.

[12]  H. Dralle,et al.  Distinct Expression of Galectin‐3 in Pheochromocytomas , 2006, Annals of the New York Academy of Sciences.

[13]  Shailesh Singh,et al.  Inhibition of cyclooxygenase-2 decreases breast cancer cell motility, invasion and matrix metalloproteinase expression , 2006, BMC Cancer.

[14]  A. Renshaw Silverberg??s Principles and Practice of Surgical Pathology and Cytopathology , 2006 .

[15]  Yin Li,et al.  [nm23-H1 gene inhibits lung cancer cell invasion through down-regulation of PKC signal pathway]. , 2006, Zhonghua zhong liu za zhi [Chinese journal of oncology].

[16]  A. Lucci,et al.  COX-2 induces IL-11 production in human breast cancer cells. , 2006, The Journal of surgical research.

[17]  B. Ning,et al.  Identification of functional genetic variants in cyclooxygenase-2 and their association with risk of esophageal cancer. , 2005, Gastroenterology.

[18]  B. Ning,et al.  Identification of Functional Genetic Variants in and Their Association With Risk of Esophageal Cancer , 2005 .

[19]  Y. Maehara,et al.  Galectin-3 expression is a potent prognostic marker in colorectal cancer. , 2005, Anticancer research.

[20]  K. Ohba,et al.  Expression of nm23-H1 gene product in sarcomatous cancer cells of renal cell carcinoma: correlation with tumor stage and expression of matrix metalloproteinase-2, matrix metalloproteinase-9, sialyl Lewis X, and c-erbB-2. , 2005, Urology.

[21]  A. Lucci,et al.  COX-2 overexpression increases motility and invasion of breast cancer cells. , 2005 .

[22]  K. Pacak,et al.  Downregulation of metastasis suppressor genes in malignant pheochromocytoma , 2005, International journal of cancer.

[23]  Yingjia Sun,et al.  [Molecular mechanism of reversing metastatic phenotype in human high-metastatic large cell lung cancer cell line L9981 by nm23-H1]. , 2005, Ai zheng = Aizheng = Chinese journal of cancer.

[24]  R. Lloyd,et al.  Role of COX-2, thromboxane A2 synthase, and prostaglandin I2 synthase in papillary thyroid carcinoma growth , 2005, Modern Pathology.

[25]  A. Piga,et al.  Galectin-3 expression in non-small cell lung carcinoma. , 2004, Cancer letters.

[26]  R. DuBois,et al.  Cyclooxygenase as a Target in Lung Cancer , 2004, Clinical Cancer Research.

[27]  Changyu Wang,et al.  Association between Nm23-H1 gene expression and metastasis of ovarian carcinoma. , 2004, Ai zheng = Aizheng = Chinese journal of cancer.

[28]  R. Kittles,et al.  Delivery technique plays an important role in determining vessel wall apposition of the Enterprise self-expanding intracranial stent , 2011, Journal of Neurointerventional Surgery.

[29]  P. Datta,et al.  Expression profile of genes associated with antimetastatic gene: nm23‐Mediated metastasis inhibition in breast carcinoma cells , 2004, International journal of cancer.

[30]  Yulian Wu,et al.  [The expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma]. , 2002, Zhonghua yi xue za zhi.

[31]  L. Thompson Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) to Separate Benign From Malignant Neoplasms: A Clinicopathologic and Immunophenotypic Study of 100 Cases , 2002, The American journal of surgical pathology.

[32]  P. Heikkilä,et al.  Increased expression of cyclooxygenase-2 in malignant pheochromocytomas. , 2001, The Journal of clinical endocrinology and metabolism.

[33]  N. Chow,et al.  The role of nm23-H1 in the progression of transitional cell bladder cancer. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[34]  F. Fitzpatrick,et al.  Cyclooxygenase-2 and carcinogenesis. , 2000, Biochimica et biophysica acta.

[35]  R. DeLellis,et al.  Principles and Practice of Surgical Pathology and Cytopathology , 1999 .

[36]  M. S. Lakshmi,et al.  Expression of metastasis-associated genes h-mts1 (S100A4) and nm23 in carcinoma of breast is related to disease progression. , 1998, DNA and cell biology.

[37]  G. Bevilacqua,et al.  Down‐regulation of the nm23.h1 gene inhibits cell proliferation , 1997, International journal of cancer.

[38]  R. Bast,et al.  Expression of the 67-kD laminin receptor, galectin-1, and galectin-3 in advanced human uterine adenocarcinoma. , 1996, Human pathology.

[39]  M J Bissell,et al.  A Novel Function for the nm23-Hl Gene: Overexpression in Human Breast Carcinoma Cells Leads to the Formation of Basement Membrane and Growth Arrest , 2010 .

[40]  H. Tashiro,et al.  Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. , 1994, Cancer research.

[41]  DeAtkine Ab,et al.  The adrenal glands. , 1991 .

[42]  G. Cahill,et al.  Tumors of the adrenal gland. , 1950, The Journal of urology.

[43]  S. Suster,et al.  Modern Surgical Pathology , 2009 .

[44]  E. Lack Tumors of the adrenal glands and extraadrenal paraganglia , 2007 .

[45]  Shun-liang Gao,et al.  Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma. , 2005, World journal of gastroenterology.

[46]  E. Bruyneel,et al.  [Cyclooxygenase 2 and carcinogenesis]. , 2004, Bulletin du cancer.

[47]  J. Sygut,et al.  Usefulness of galectin-3 immunohistochemistry in differential diagnosis between thyroid follicular carcinoma and follicular adenoma. , 2003, Polish journal of pathology : official journal of the Polish Society of Pathologists.

[48]  K. Kovacs,et al.  An immunohistochemical survey of nine cases of medullary carcinoma of thyroid including reactivity for Cox-1 and Cox-2 enzymes , 2002, Endocrine pathology.

[49]  Sevin [Adrenal glands]. , 1959, Produits pharmaceutiques.

[50]  F. Hartman,et al.  The adrenal gland , 1949 .