Low HtrA1 expression in patients with long‑standing ulcerative colitis and colorectal cancer

Altobelli,Emma; Latella,Giovanni; Morroni,Manrico; Licini,Caterina; Tossetta,Giovanni; Mazzucchelli,Roberta; Profeta,Valerio F.; Coletti,Gino; Leocata,Pietro; Castellucci,Mario; Guerrieri,Mario; Petrocelli,Reimondo; De Berardis,Berardo; De Padova,Marina; Di Leonardo,Gabriella; Paladini,Antonella; Mignosi,Filippo; Quaglione,Gina; Fagnano,Roberto; Marzioni,Daniela

doi:10.3892/or.2017.5700

Low HtrA1 expression in patients with long‑standing ulcerative colitis and colorectal cancer

Authors:
- Emma Altobelli
- Giovanni Latella
- Manrico Morroni
- Caterina Licini
- Giovanni Tossetta
- Roberta Mazzucchelli
- Valerio F. Profeta
- Gino Coletti
- Pietro Leocata
- Mario Castellucci
- Mario Guerrieri
- Reimondo Petrocelli
- Berardo De Berardis
- Marina De Padova
- Gabriella Di Leonardo
- Antonella Paladini
- Filippo Mignosi
- Gina Quaglione
- Roberto Fagnano
- Daniela Marzioni
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Affiliations: Epidemiology and Biostatistics Unit, Teramo, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy, Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy, Department of Experimental and Clinical Medicine, Università Politecnica Delle Marche, Ancona, Italy, Pathological Anatomy, Department of Medical Sciences and Public Health, Università Politecnica Delle Marche, United Hospitals, Ancona, Italy, Department of Community Health, Teramo, Italy, Pathology Unit, San Salvatore Hospital, L’Aquila, Italy, Pathology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy, Unit of Surgery, Università Politecnica delle Marche, Ospedali Riuniti, Ancona, Italy, Community Health, ASREM, Molise, Italy, Unit of Surgery, Mazzini Hospital, Teramo, Italy, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy, Department of Information Engineering, Computer Science and Mathematics, University of L'Aquila, L'Aquila, Italy, Pathology Unit, Mazzini Hospital, Teramo, Italy, ASL, Teramo, Italy
Published online on: June 6, 2017 https://doi.org/10.3892/or.2017.5700
Pages: 418-426

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Abstract

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is being increasingly investigated. HtrA1 overexpression inhibits cell growth and proliferation by influencing apoptosis, invasiveness and migration of tumour cells. In the present study, HtrA1 expression was analysed in 228 colon tissue samples from patients with CRC, adenoma with high-grade dysplasia (AHD), adenoma with low-grade dysplasia (ALD), ulcerative colitis of >10 year duration (UCL), ulcerative colitis of <5 year duration (UCS) and colonic diverticulitis (D), and was compared with its expression in normal colon tissues (NCTs) collected 5 cm from the CRC lesion and in healthy colon mucosa (HC), to establish whether HtrA1 can serve as a biomarker for these conditions. All tissue specimens came from Italian Caucasian subjects. The main finding of the present study was that HtrA1 expression was significantly reduced in CRC and UCL tissues compared with that observed in both NCT and HC samples and with tissues from the other patients. In particular, a similar HtrA1 expression was detected in the stromal compartment of UCL and CRC samples. In contrast, the HtrA1 level was significantly lower (p=0.0008) in UCL compared with UCS tissues, suggesting an inverse relationship between HtrA1 expression and ulcerative colitis duration. HtrA1 immunostaining in the stromal compartment of AHD and ALD tissues showed no differences compared with the HC tissues. No data are available on the immunohistochemical localization of HtrA1 in CRC or IBD. The present findings suggest that HtrA1 could serve as a marker to identify UCL patients at high risk of developing CRC.

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