Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2015

Open Access 01-12-2015 | Research

Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer

Authors: Iván Roa, Gonzalo de Toro, Fernanda Fernández, Anakaren Game, Sergio Muñoz, Xabier de Aretxabala, Milind Javle

Published in: Diagnostic Pathology | Issue 1/2015

Login to get access

Abstract

Background

PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC.

Methods

The immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor.

Results

The group was comprised of 108 patients, 91 women (84.3 %) and 17 men (15.7 %) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33 %) were early carcinomas (EC) and the remaining 73 (67 %) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3 %). Only in three AC (4.1 %) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53 % at 10 months.

Discussion

Loss of PTEN expression was observed in 4.1 % of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.
Literature
1.
Eslick GD. Epidemiology of gallbladder cancer. Gastroenterol Clin N Am. 2010;39(2):307–30. ix.CrossRef
2.
3.
Andia ME, Hsing AW, Andreotti G, Ferreccio C. Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study. Int J Cancer. 2008;123(6):1411–6.PubMedCentralCrossRefPubMed
4.
5.
Goldin RD, Roa JC. Gallbladder cancer: a morphological and molecular update. Histopathology. 2009;55(2):218–29.CrossRefPubMed
6.
Lazcano-Ponce EC, Miquel JF, Munoz N, Herrero R, Ferrecio C, Wistuba II, et al. Epidemiology and molecular pathology of gallbladder cancer. CA Cancer J Clin. 2001;51(6):349–64.CrossRefPubMed
7.
Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer. 2004;4(9):695–706.CrossRefPubMed
8.
Wistuba II, Tang M, Maitra A, Alvarez H, Troncoso P, Pimentel F, et al. Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma. Cancer Res. 2001;61(9):3795–800.PubMed
9.
Steck PA, Pershouse MA, Jasser SA, Yung WK, Lin H, Ligon AH, et al. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers. Nat Genet. 1997;15(4):356–62.CrossRefPubMed
10.
Ji X, Tang J, Halberg R, Busam D, Ferriera S, Pena MM, et al. Distinguishing between cancer driver and passenger gene alteration candidates via cross-species comparison: a pilot study. BMC Cancer. 2010;10:426.PubMedCentralCrossRefPubMed
11.
12.
Jiao Y, Pawlik TM, Anders RA, Selaru FM, Streppel MM, Lucas DJ, et al. Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas. Nat Genet. 2013;45(12):1470–3.PubMedCentralCrossRefPubMed
13.
Li M, Zhang Z, Li X, Ye J, Wu X, Tan Z, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway. Nat Genet. 2014;46(8):872–6. doi:10.​1038/​ng.​3030.CrossRefPubMed
14.
15.
Carracedo A, Alimonti A, Pandolfi PP. PTEN level in tumor suppression: how much is too little? Cancer Res. 2008;71(3):629–33.CrossRef
16.
17.
Ocana A, Vera-Badillo F, Al-Mubarak M, Templeton AJ, Corrales-Sanchez V, Diez-Gonzalez L, et al. Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: systematic review and meta-analysis. PLoS One. 2014;9(4):e95219.PubMedCentralCrossRefPubMed
18.
Shuch B, Ricketts CJ, Vocke CD, Komiya T, Middelton LA, Kauffman EC, et al. Germline PTEN mutation Cowden syndrome: an underappreciated form of hereditary kidney cancer. J Urol. 2013;190(6):1990–8.PubMedCentralCrossRefPubMed
19.
20.
Chang SK, Liang WT, Thamboo TP. Inflammatory pseudotumour arising from periampullary carcinoid: a “cancer-like” tumour in a “fake” tumour. Singap Med J. 2009;50(3):e100–1.
21.
Lavorato-Rocha AM, Anjos LG, Cunha IW, Vassallo J, Soares FA, Rocha RM. Immunohistochemical assessment of PTEN in vulvar cancer: Best practices for tissue staining, evaluation, and clinical association. Methods. 2014;77-78:20–4.CrossRef
22.
Sakr RA, Barbashina V, Morrogh M, Chandarlapaty S, Andrade VP, Arroyo CD, et al. Protocol for PTEN expression by immunohistochemistry in formalin-fixed paraffin-embedded human breast carcinoma. Appl Immunohistochem Mol Morphol. 2010;18(4):371–4.PubMedCentralCrossRefPubMed
23.
Taylor CR. Quantifiable internal reference standards for immunohistochemistry: the measurement of quantity by weight. Appl Immunohistochem Mol Morphol. 2006;14(3):253–9.CrossRefPubMed
24.
Djordjevic B, Hennessy BT, Li J, Barkoh BA, Luthra R, Mills GB, et al. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol. 2012;25(5):699–708.PubMedCentralCrossRefPubMed
25.
Keniry M, Parsons R. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene. 2008;27(41):5477–85.CrossRefPubMed
26.
Cheung LW, Hennessy BT, Li J, Yu S, Myers AP, Djordjevic B, et al. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability. Cancer Discov. 2011;1(2):170–85.PubMedCentralCrossRefPubMed
27.
De Luca A, Maiello MR, D’Alessio A, Pergameno M, Normanno N. The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets. 2012;16 Suppl 2:S17–27.CrossRefPubMed
28.
Soria JC, Lee HY, Lee JI, Wang L, Issa JP, Kemp BL, et al. Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation. Clin Cancer Res. 2002;8(5):1178–84.PubMed
29.
Saal LH, Gruvberger-Saal SK, Persson C, Lovgren K, Jumppanen M, Staaf J, et al. Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair. Nat Genet. 2008;40(1):102–7.PubMedCentralCrossRefPubMed
30.
Liu DC, Yang ZL. Overexpression of EZH2 and loss of expression of PTEN is associated with invasion, metastasis, and poor progression of gallbladder adenocarcinoma. Pathol Res Pract. 2011;207(8):472–8.CrossRefPubMed
31.
32.
Butte JM, Torres J, Veras EF, Matsuo K, Gönen M, D’Angelica MI, et al. Regional Differences in Gallbladder Cancer Pathogenesis: Insights from a Comparison of Cell Cycle-Regulatory, PI3K, and Pro-Angiogenic Protein Expression. Ann Surg Oncol. 2013;20(5):1470-81.
33.
Li Q, Yang Z. Expression of phospho-ERK1/2 and PI3-K in benign and malignant gallbladder lesions and its clinical and pathological correlations. J Exp Clin Cancer Res. 2009;28:65.PubMedCentralCrossRefPubMed
34.
Lunardi A, Webster KA, Papa A, Padmani B, Clohessy JG, Bronson RT, et al. Role of aberrant PI3K pathway activation in gallbladder tumorigenesis. Oncotarget. 2014;5(4):894–900.PubMedCentralPubMed
35.
Zong H, Yin B, Zhou H, Cai D, Ma B, Xiang Y. Inhibition of mTOR pathway attenuates migration and invasion of gallbladder cancer via EMT inhibition. Mol Biol Rep. 2014;41(7):4507–12.CrossRefPubMed
36.
Dienstmann R, Rodon J, Serra V, Tabernero J. Picking the point of inhibition: a comparative review of PI3K/AKT/mTOR pathway inhibitors. Mol Cancer Ther. 2014;13(5):1021–31.CrossRefPubMed
37.
Costello BA, Borad MJ, Qi Y, Kim GP, Northfelt DW, Erlichman C, et al. Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors. Investig New Drugs. 2014;32(4):710–6.CrossRef
Metadata
Title
Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer
Authors
Iván Roa
Gonzalo de Toro
Fernanda Fernández
Anakaren Game
Sergio Muñoz
Xabier de Aretxabala
Milind Javle
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2015
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/s13000-015-0381-2

Other articles of this Issue 1/2015

Diagnostic Pathology 1/2015 Go to the issue

Research

High microRNA-23a expression in laryngeal squamous cell carcinoma is associated with poor patient prognosis

Research

Gene-expression analysis of a colorectal cancer-specific discriminatory transcript set on formalin-fixed, paraffin-embedded (FFPE) tissue samples

Research

RETRACTED ARTICLE: Effect of platelet-rich plasma on the healing of cutaneous defects exposed to acute to chronic wounds: a clinico-histopathologic study in rabbits

Research

Prognostic significance of FAM3C in esophageal squamous cell carcinoma

Research

Clinicopathologic features of plasmablastic lymphoma: Single-center series of 8 cases from Saudi Arabia

Research

Histological study of chronic pulmonary aspergillosis