title: PROX1 is involved in progression of rectal neuroendocrine tumors, NETs.
abstract: PROX1 is a homeobox transcription factor involved in the development of the lens, liver and heart and found upregulated in colorectal cancers. We studied PROX1 expression by immunohistochemistry in rectal neuroendocrine tumors (NETs). Approximately 10 to 15 % of gastroenteropancreatic NETs occur in the rectum, and some may metastasize. Yet little is known about the molecular pathogenesis of rectal NETs or their metastasis propensity. The objectives were to find out whether PROX1 plays a role in progression of rectal NETs and whether it has value as prognostic marker. In grading of rectal NETs, we applied the WHO 2010 classification. We carried out immunohistochemical staining of PROX1 on 72 primary tumors and six metastases and evaluated nuclear positivity in each tumor. Correlation between PROX1 expression, metastasis and patient survival was then assessed. Annexin A1, a downstream target of PROX1, was immunohistochemically assessed in 18 tumors. PROX1 protein was detected in about half of the tumors, with stronger expression in metastasized cases. PROX1 expression correlated with tumor metastasis and patient prognosis. Annexin A1 was negative in most of the high-grade tumors correlating strongly with grade and metastatic potential. Our results indicate that immunohistochemical detection of PROX1 correlates with a more malignant phenotype in rectal NETs. High PROX1 expression was associated with increased metastatic potential and poor patient survival but not as strongly as grade by the WHO 2010 classification. PROX1 may be involved in progression of rectal NETs as a part of the Wnt pathway.
authors.affiliation: Department of Pathology, University of Helsinki and Huslab, 00014, Helsinki, Finland, juha.jernman@gmail.com.
authors.forename: Juha
authors.initials: J
authors.lastname: Jernman
authors.forename: Pauliina
authors.initials: P
authors.lastname: Kallio
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.forename: Matti J
authors.initials: MJ
authors.lastname: Välimäki
authors.forename: Hannu
authors.initials: H
authors.lastname: Haapasalo
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology*; D012004:Rectal Neoplasms / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein