Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer
Open accessAbstract
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.
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Inactivated PTEN has been found in various human cancers such as prostate cancer, breast cancer, and brain cancer (glioblastoma).
“Inactivated PTEN has been found in various human cancers such as prostate cancer, breast cancer, and brain cancer (glioblastoma) (Roa et al. 2015).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Roa et al. 2015
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Cites
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
Steck, P. A., Pershouse, M. A., Jasser, S. A., Yung, W. K. A., Lin, H., Ligon, A. H., Langford, L. A., Baumgard, M. L., Hattier, T., Davis, T., et al. (1997) · Nature Genetics · doi:10.1038/ng0497-356 · Cited by 2,742 · see citing works
PTEN and the PI3-Kinase Pathway in Cancer
Chalhoub, N., & Baker, S. J. (2008) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092311 · Cited by 1,245 · see citing works
Gallbladder cancer: epidemiology and outcome
Shaffer, E. A., & Hundal, R. (2014) · Clinical Epidemiology · doi:10.2147/clep.s37357 · Cited by 1,088 · see citing works
Tenets of PTEN Tumor Suppression
Salmena, L., Carracedo, A., & Pandolfi, P. P. (2008) · Cell · doi:10.1016/j.cell.2008.04.013 · Cited by 1,027 · see citing works
Epidemiology and Molecular Pathology of Gallbladder Cancer
Lazcano-Ponce, E. C., Miquel, J. F., Munoz, N., Herrero, R., Ferrecio, C., Wistuba, I. I., de Ruíz, P. A., Urista, G. A., & Nervi, F. O. (2001) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.51.6.349 · Cited by 866 · see citing works
Luca, A. D., Maiello, M. R., D’Alessio, A., Pergameno, M., & Normanno, N. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.639361 · Cited by 737 · see citing works
Jiao, Y., Pawlik, T. M., Anders, R. A., Selaru, F. M., Streppel, M. M., Lucas, D. J., Niknafs, N., Guthrie, V. B., Maitra, A., Argani, P., et al. (2013) · Nature Genetics · doi:10.1038/ng.2813 · Cited by 689 · see citing works
Cheung, L. W. T., Hennessy, B. T., Li, J., Yu, S., Myers, A. P., Djordjevic, B., Lu, Y., Stemke‐Hale, K., Dyer, M. D., Zhang, F., et al. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0039 · Cited by 469 · see citing works
Picking the Point of Inhibition: A Comparative Review of PI3K/AKT/mTOR Pathway Inhibitors
Dienstmann, R., Rodon, J. A., Serra, V., & Tabernero, J. M. (2014) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-13-0639 · Cited by 464 · see citing works
Gallbladder cancer: lessons from a rare tumour
Wistuba, I. I., & Gazdar, A. F. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1429 · Cited by 453 · see citing works
Li, M., Zhang, Z., Li, X., Ye, J., Wu, X., Tan, Z., Liu, C., Shen, B., Wang, X.-A., Wu, W., et al. (2014) · Nature Genetics · doi:10.1038/ng.3030 · Cited by 441 · see citing works
Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation.
Soria, J., Lee, H., Lee, J. I., Luo, W., Issa, J. J., Kemp, B. L., Liu, D. D., Kurie, J. M., Mao, L., & Khuri, F. R. (2002) · PubMed · Cited by 406 · see citing works
The role of PTEN signaling perturbations in cancer and in targeted therapy
Keniry, M. E., & Parsons, R. E. (2008) · Oncogene · doi:10.1038/onc.2008.248 · Cited by 358 · see citing works
Saal, L. H., Gruvberger-Saal, S. K., Persson, C., Lövgren, K., Jumppanen, M., Staaf, J., Jönsson, G. B., Pires, M. M., Maurer, M., Holm, K., et al. (2007) · Nature Genetics · doi:10.1038/ng.2007.39 · Cited by 357 · see citing works
PTEN Level in Tumor Suppression: How Much Is Too Little?
Carracedo, A., Alimonti, A., & Pandolfi, P. P. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-2488 · Cited by 244 · see citing works
Gallbladder cancer: a morphological and molecular update
Goldin, R. D., & Roa, J. C. (2009) · Histopathology · doi:10.1111/j.1365-2559.2008.03192.x · Cited by 196 · see citing works
Djordjevic, B., Hennessy, B. T., Li, J., Barkoh, B. A., Luthra, R., Mills, G. B., & Broaddus, R. R. (2012) · Modern Pathology · doi:10.1038/modpathol.2011.208 · Cited by 175 · see citing works
Ocaña, A., Vera-Badillo, F., Al-Mubarak, M., Templeton, A. J., Corrales‐Sánchez, V., Díez-González, L., Cuenca-López, M. D., Šeruga, B., Pandiella, A., & Amir, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095219 · Cited by 168 · see citing works
Andía, M. E., Hsing, A. W., Andreotti, G., & Catterina Ferreccio, R. (2008) · International Journal of Cancer · doi:10.1002/ijc.23662 · Cited by 104 · see citing works
Germline PTEN Mutation Cowden Syndrome: An Underappreciated Form of Hereditary Kidney Cancer
Shuch, B. M., Ricketts, C. J., Vocke, C. D., Komiya, T., Middelton, L. A., KAUFFMAN, E. C., Merino, M. J., Metwalli, A. R., Dennis, P. A., & Linehan, W. M. (2013) · The Journal of Urology · doi:10.1016/j.juro.2013.06.012 · Cited by 104 · see citing works
Epidemiology of Gallbladder Cancer
Eslick, G. D. (2010) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2010.02.011 · Cited by 86 · see citing works
Zong, H., Yin, B., Zhou, H., Cai, D., Ma, B., & Xiang, Y. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3321-4 · Cited by 75 · see citing works
PTEN modulators: a patent review
Boosani, C. S., & Agrawal, D. K. (2013) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2013.768985 · Cited by 70 · see citing works
Genome-wide allelotyping analysis reveals multiple sites of allelic loss in gallbladder carcinoma.
Wistuba, I. I., Tang, M., Maitra, A., Alvarez, H., Troncoso, P., Pimentel, F., & Gazdar, A. F. (2001) · PubMed · Cited by 68 · see citing works
Sakr, R. A., Barbashina, V., Morrogh, M., Chandarlapaty, S., de Andrade, V. P., Arroyo, C. D., Olvera, N., & King, T. A. (2010) · Applied immunohistochemistry & molecular morphology · doi:10.1097/pai.0b013e3181d50bd5 · Cited by 61 · see citing works
Role of aberrant PI3K pathway activation in gallbladder tumorigenesis
Lunardi, A., Webster, K. A., Papa, A., Padmani, B., Clohessy, J. G., Bronson, R. T., & Pandolfi, P. P. (2014) · Oncotarget · doi:10.18632/oncotarget.1808 · Cited by 59 · see citing works
Phase I trial of everolimus, gemcitabine and cisplatin in patients with solid tumors
Costello, B. A., Borad, M. J., Qi, Y., Kim, G. P., Northfelt, D., Erlichman, C., & Alberts, S. R. (2014) · Investigational New Drugs · doi:10.1007/s10637-014-0096-3 · Cited by 57 · see citing works
Quantifiable Internal REFERENCE Standards for Immunohistochemistry
Taylor, C. R. (2006) · Applied immunohistochemistry & molecular morphology · doi:10.1097/00129039-200609000-00001 · Cited by 52 · see citing works
Li, Q., & Yang, Z. (2009) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/1756-9966-28-65 · Cited by 52 · see citing works
Liu, D.-C., & Yang, Z. (2011) · Pathology - Research and Practice · doi:10.1016/j.prp.2011.05.010 · Cited by 50 · see citing works
Lavorato-Rocha, A. M., dos Anjos, L. G., da Cunha, I. W., Vassallo, J., Soares, F. A., & Rocha, R. M. (2015) · Methods · doi:10.1016/j.ymeth.2014.12.017 · Cited by 31 · see citing works
Achieving cancer cell death with PI3K/mTOR‐targeted therapies
Yea, S. S., & Fruman, D. A. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12028 · Cited by 28 · see citing works
Ji, X., Tang, J., Halberg, R. B., Busam, D., Ferriera, S., Peña, M. M. O., Venkataramu, C. R., Yeatman, T. J., & Zhao, S. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-426 · Cited by 20 · see citing works
Butte, J. M., Torres, J., Veras, E. F. T., Matsuo, K., Gönen, M., D'Angelica, M. I., Waugh, E., Meneses, M. F., Inayama, Y., Fong, Y., et al. (2012) · Annals of Surgical Oncology · doi:10.1245/s10434-012-2761-0 · Cited by 10 · see citing works
Chang, S. K. Y., Liang, W., & Thamboo, T. P. (2009) · PubMed · Cited by 2 · see citing works
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Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638 · see citing works
Corti, F., Nichetti, F., Raimondi, A., Niger, M., Prinzi, N., Torchio, M., Tamborini, E., Perrone, F., Pruneri, G., Bartolomeo, M. D., et al. (2018) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2018.11.001 · Cited by 129 · see citing works
Liu, R., Liao, X., Pan, M., Tang, J., Chen, S., Zhang, Y., Lu, P., Lu, L. J., Zou, Y., Qin, X., et al. (2019) · The Journal of Immunology · doi:10.4049/jimmunol.1801166 · Cited by 108 · see citing works
Li, X., Teng, S., Zhang, Y., Zhang, W., Zhang, X., Xu, K., Yao, H., Yao, J., Wang, H., Liang, X., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.16789 · Cited by 91 · see citing works
Reviewing cancer’s biology: an eclectic approach
DIORI, I. K., & Şanlıer, Ş. H. (2021) · Journal of the Egyptian National Cancer Institute · doi:10.1186/s43046-021-00088-y · Cited by 52 · see citing works
Arun, R. P., Sivanesan, D., Vidyasekar, P., & Verma, R. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-06416-4 · Cited by 52 · see citing works
Doghish, A. S., Midan, H. M., Elbadry, A. M. M., Darwish, S. F., Rizk, N. I., Ziada, B. O., Elbokhomy, A. S., Elrebehy, M. A., Elballal, M. S., El‐Husseiny, H. M., et al. (2023) · Pathology - Research and Practice · doi:10.1016/j.prp.2023.154682 · Cited by 33 · see citing works
Jiang, T., Feng, X., Zheng, F., Cui, X.-W., Lin, Y., Pan, Y., Yang, C., Ding, Z., Zhang, Y., Tan, Y., et al. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.11.016 · Cited by 26 · see citing works
Liang, H., Sun, L., & Liu, N. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.122 · Cited by 25 · see citing works
RetractedEpigenetic Downregulation of PTEN in Gallbladder Cancer
Tekcham, D. S., Gupta, S., Shrivastav, B. R., & Tiwari, P. K. (2017) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-017-9919-8 · Cited by 20 · see citing works
Erlangga, Z., Wolff, K., Poth, T., Peltzer, A., Nahnsen, S., Spielberg, S., Timrott, K., Woller, N., Kühnel, F., Manns, M. P., et al. (2019) · Cancers · doi:10.3390/cancers11121904 · Cited by 14 · see citing works
Contemporary Tailored Oncology Treatment of Biliary Tract Cancers
Turkes, F., Carmichael, J. A., Cunningham, D., & Starling, N. (2019) · Gastroenterology Research and Practice · doi:10.1155/2019/7698786 · Cited by 12 · see citing works
Chiang, N., Chen, L., Shan, Y., Yeh, C., & Chen, M. (2021) · Biomolecules · doi:10.3390/biom11010097 · Cited by 10 · see citing works
Monteiro, R., Hallikeri, K., & Sudhakaran, A. (2021) · Journal of Oral and Maxillofacial Research · doi:10.5037/jomr.2021.12103 · Cited by 10 · see citing works
Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor
He, T., Zhang, X., Hao, J., & Ding, S. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.684529 · Cited by 10 · see citing works
Global perspective on the genetic, epigenetic, and transcriptomic basis of gallbladder cancer
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Sztankovics, D., Krencz, I., Moldvai, D., Dankó, T., Nagy, Á., Nagy, N., Bedics, G., Rókusz, A., Papp, G., Tõkés, A., et al. (2023) · Scientific Reports · doi:10.1038/s41598-023-46927-x · Cited by 8 · see citing works
Targeting phosphoinositide‐3‐kinase pathway in biliary tract cancers: A remedial route?
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Long, C., Jian, J., Li, X., Wang, G., & Wang, J. (2017) · Oncology Letters · doi:10.3892/ol.2017.5689 · Cited by 5 · see citing works
Gallbladder Cancer: Epigenetic Landscape, Targeted Therapy, and Prospect of Epitherapy
Sharma, N., Tomar, A., & Tiwari, P. K. (2023) · Springer eBooks · doi:10.1007/978-981-19-6442-8_12 · Cited by 4 · see citing works
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- Authors
- Roa, I., de Toro, G., Fernández, F., Game, A., Muñoz, S., de Aretxabala, X., & Javle, M.
- Affiliations
- Universidad del Desarrollo (CL)
- Universidad de La Frontera (CL)
- The University of Texas MD Anderson Cancer Center (US)
- Venue
- Diagnostic Pathology
- Published
- 2015-08-21
- Volume
- 10
- Issue
- 1
- Pages
- 148-148
- ISSN
- 1746-1596 (ISSN-L)
- PMC
- PMC4546176
- OpenAlex
- W1823362496
- Cited by
- 22
- References
- 36
- Citations by year
- 2025: 2 · 2023: 5 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 4
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Diagnostic Pathology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Omeka S (Universidad de La Frontera) (submittedVersion, cc-by-nc-nd)
- Funders
- Fondecyt (1120208)
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gallbladder and Bile Duct Disorders
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- PTEN, tumor suppressor inactivation, gallbladder cancer, prognosis, survival, tumor differentiation, tumor infiltration
- MeSH terms
- Adenocarcinoma, Adult, Aged, Aged, 80 and over, Female, Gallbladder Neoplasms, Humans, Immunohistochemistry, Male, Middle Aged, Prognosis, Biomarkers, Tumor, Genes, Tumor Suppressor, PTEN Phosphohydrolase, Kaplan-Meier Estimate
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