MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder

Liu,Ziru; Yang,Zhulin; Jiang,Song; Zou,Qiong; Yuan,Yuan; Li,Jinghe; Li,Daiqiang; Liang,Lufeng; Chen,Meigui; Chen,Senlin

doi:10.3892/mmr.2016.5851

MCM2 and TIP30 are prognostic markers in squamous cell/adenosquamous carcinoma and adenocarcinoma of the gallbladder

Authors:
- Ziru Liu
- Zhulin Yang
- Song Jiang
- Qiong Zou
- Yuan Yuan
- Jinghe Li
- Daiqiang Li
- Lufeng Liang
- Meigui Chen
- Senlin Chen
View Affiliations

Affiliations: Department of Minimal Invasive Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Research Laboratory of Hepatobiliary Diseases, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Pathology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Department of Pathology, Basic School of Medicine, Changsha, Hunan 410078, P.R. China, Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, Hunan Provincial People's Hospital, Changsha, Hunan 410007, P.R. China, Department of Pathology, Loudi Central Hospital, Loudi, Hunan 417011, P.R. China, Department of Pathology, Hunan Provincial Tumor Hospital, Changsha, Hunan 410013, P.R. China
Published online on: October 13, 2016 https://doi.org/10.3892/mmr.2016.5851
Pages: 4581-4592
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The clinicopathological and biological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder remain to be fully elucidated, due to the fact that it is a rare gallbladder cancer subtype. In the current study, the expression of minichromosome maintenance complex component 2 (MCM2) and HIV‑1 tat interactive protein 2 (TIP30) was measured in 46 cases of SC/ASC and 80 adenocarcinomas (AC) using immunohistochemistry. Positive MCM2 and negative TIP30 expression were significantly associated with large tumor size, high TNM stage, invasion, lymph node metastasis and lack of surgical curability in SC/ASC and AC. Positive MCM2 and negative TIP30 expression were significantly associated with poor differentiation in AC, whereas only MCM2 was correlated with differentiation in SC/ASC. Univariate Kaplan‑Meier analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and surgical curability were significantly associated with post‑operative survival in patients with SC/ASC and AC. Multivariate Cox regression analysis demonstrated that positive MCM2 and negative TIP30 expression, the degree of differentiation, tumor size, TNM stage, invasion, lymph node metastasis and lack of surgical curability were also independent predictors of poor prognosis in patients with SC/ASC and AC. These data suggest that positive MCM2 and negative TIP30 expression are closely correlated with the clinical, pathological and biological parameters, in addition to poor prognosis in patients with gallbladder cancer.

View Figures

View References

1	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar : PubMed/NCBI
2	Jayaraman S and Jarnagin WR: Management of gallbladder cancer. Gastroenterol Clin North Am. 39:331–342. 2010. View Article : Google Scholar : PubMed/NCBI
3	Reid KM, Ramos-De la Medina A and Donohue JH: Diagnosis and surgical management of gallbladder cancer: A review. J Gastrointest Surg. 11:671–681. 2007. View Article : Google Scholar : PubMed/NCBI
4	Hawkins WG, DeMatteo RP, Jarnagin WR, Ben-Porat L, Blumgart LH and Fong Y: Jaundice predicts advanced disease and early mortality in patients with gallbladder cancer. Ann Surg Oncol. 11:310–315. 2004. View Article : Google Scholar : PubMed/NCBI
5	Ootani T, Shirai Y, Tsukada K and Muto T: Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder. Cancer. 69:2647–2652. 1992. View Article : Google Scholar : PubMed/NCBI
6	Roa JC, Tapia O, Cakir A, Basturk O, Dursun N, Akdemir D, Saka B, Losada H, Bagci P and Adsay NV: Squamous cell and adenosquamous carcinomas of the gallbladder: Clinicopathological analysis of 34 cases identified in 606 carcinomas. Mod Pathol. 24:1069–1078. 2011. View Article : Google Scholar : PubMed/NCBI
7	Park SB, Kim YH, Rho HL, Chae GB and Hong SK: Primary carcinosarcoma of the gallbladder. J Korean Surg Soc. 82:54–58. 2012. View Article : Google Scholar : PubMed/NCBI
8	Liu DC and Yang ZL: MTDH and EphA7 are markers for metastasis and poor prognosis of gallbladder adenocarcinoma. Diagn Cytopathol. 41:199–205. 2013. View Article : Google Scholar : PubMed/NCBI
9	Giaginis C, Vgenopoulou S, Vielh P and Theocharis S: MCM proteins as diagnostic and prognostic tumor markers in the clinical setting. Histol Histopathol. 25:351–370. 2010.PubMed/NCBI
10	MacCallum DE and Hall PA: The biochemical characterization of the DNA binding activity of pKi67. J Pathol. 191:286–298. 2000. View Article : Google Scholar : PubMed/NCBI
11	Mehrotra P, Gonzalez MA, Johnson SJ, Coleman N, Wilson JA, Davies BR and Lennard TW: Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy. Laryngoscope. 116:1434–1438. 2006. View Article : Google Scholar : PubMed/NCBI
12	Brown DC and Gatter KC: Ki67 protein: The immaculate deception? Histopathology. 40:2–11. 2002. View Article : Google Scholar : PubMed/NCBI
13	Toschi L and Bravo R: Changes in cyclin/proliferating cell nuclear antigen distribution during DNA repair synthesis. J Cell Biol. 107:1623–1628. 1988. View Article : Google Scholar : PubMed/NCBI
14	Tachibana KE, Gonzalez MA and Coleman N: Cell-cycle-dependent regulation of DNA replication and its relevance to cancer pathology. J Pathol. 205:123–129. 2005. View Article : Google Scholar : PubMed/NCBI
15	Stoeber K, Tlsty TD, Happerfield L, Thomas GA, Romanov S, Bobrow L, Williams ED and Williams GH: DNA replication licensing and human cell proliferation. J Cell Sci. 114:2027–2041. 2001.PubMed/NCBI
16	Madine MA, Swietlik M, Pelizon C, Romanowski P, Mills AD and Laskey RA: The roles of the MCM, ORC, and Cdc6 proteins in determining the replication competence of chromatin in quiescent cells. J Struct Biol. 129:198–210. 2000. View Article : Google Scholar : PubMed/NCBI
17	Chatrath P, Scott IS, Morris LS, Davies RJ, Rushbrook SM, Bird K, Vowler SL, Grant JW, Saeed IT, Howard D, et al: Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epithelial lesions. Br J Cancer. 89:1048–1054. 2003. View Article : Google Scholar : PubMed/NCBI
18	Davies RJ, Freeman A, Morris LS, Bingham S, Dilworth S, Scott I, Laskey RA, Miller R and Coleman N: Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool. Lancet. 359:1917–1919. 2002. View Article : Google Scholar : PubMed/NCBI
19	Sirieix PS, O'Donovan M, Brown J, Save V, Coleman N and Fitzgerald RC: Surface expression of minichromosome maintenance proteins provides a novel method for detecting patients at risk for developing adenocarcinoma in Barrett's esophagus. Clin Cancer Res. 9:2560–2566. 2003.PubMed/NCBI
20	Zhao J, Zhang X, Shi M, Xu H, Jin J, Ni H, Yang S, Dai J, Wu M and Guo Y: TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in combination with 5-FU. Hepatology. 44:205–215. 2006. View Article : Google Scholar : PubMed/NCBI
21	Shtivelman E: A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma. Oncogene. 14:2167–2673. 1997. View Article : Google Scholar : PubMed/NCBI
22	NicAmhlaoibh R and Shtivelman E: Metastasis suppressor CC3 inhibits angiogenic properties of tumor cells in vitro. Oncogene. 20:270–275. 2001. View Article : Google Scholar : PubMed/NCBI
23	Xiao H, Palhan V, Yang Y and Roeder RG: TIP30 has an intrinsic kinase activity required for up-regulation of a subset of apoptotic genes. EMBO J. 19:956–963. 2000. View Article : Google Scholar : PubMed/NCBI
24	Li X, Zhang Y, Cao S, Chen X, Lu Y, Jin H, Sun S, Chen B, Liu J, Ding J, et al: Reduction of TIP30 correlates with poor prognosis of gastric cancer patients and its restoration drastically inhibits tumor growth and metastasis. Int J Cancer. 124:713–721. 2009. View Article : Google Scholar : PubMed/NCBI
25	Ito M, Jiang C, Krumm K, Zhang X, Pecha J, Zhao J, Guo Y, Roeder RG and Xiao H: TIP30 deficiency increases susceptibility to tumorigenesis. Cancer Res. 63:8763–8767. 2003.PubMed/NCBI
26	Nishihara K, Nagai E, Izumi Y, Yamaguchi K and Tsuneyoshi M: Adenosquamous carcinoma of the gallbladder: A clinicopathological, immunohistochemical and flow-cytometric study of twenty cases. Jpn J Cancer Res. 85:389–399. 1994. View Article : Google Scholar : PubMed/NCBI
27	Kondo M, Dono K, Sakon M, Shimizu J, Nagano H, Nakamori S, Umeshita K, Wakasa K and Monden M: Adenosquamous carcinoma of the gallbladder. Hepatogastroenterology. 49:1230–1234. 2002.PubMed/NCBI
28	Tye BK: MCM proteins in DNA replication. Annu Rev Biochem. 68:649–686. 1999. View Article : Google Scholar : PubMed/NCBI
29	Lei M and Tye BK: Initiating DNA synthesis from recruiting to activating the MCM complex. J Cell Sci. 114:1447–1454. 2001.PubMed/NCBI
30	Zhang H, Zhang Y, Duan HO, Kirley SD, Lin SX, McDougal WS, Xiao H and Wu CL: TIP30 is associated with progression and metastasis of prostate cancer. Int J Cancer. 123:810–816. 2008. View Article : Google Scholar : PubMed/NCBI
31	Zhao J, Ni H, Ma Y, Dong L, Dai J, Zhao F, Yan X, Lu B, Xu H and Guo Y: TIP30/cc3 expression in breast carcinoma: Relation to metastasis, clinicopathologic parameters, and P53 expression. Hum Pathol. 38:293–298. 2007. View Article : Google Scholar : PubMed/NCBI
32	Gakiopoulou H, Korkolopoulou P, Levidou G, Thymara I, Saetta A, Piperi C, Givalos N, Vassilopoulos I, Ventouri K, Tsenga A, et al: Minichromosome maintenance 2 and 5 in non-benign epithelial ovarian tumours: Relationship with cell cycle regulators and prognostic implications. Br J Cancer. 97:1124–1134. 2007. View Article : Google Scholar : PubMed/NCBI
33	Reena RM, Mastura M, Siti-Aishan AM, Munirah MA, Norlia A, Naqiyah I, Rohaizak M and Sharifah NA: Minichromosome maintenance 2 is a reliable proliferative marker in breast carcinoma. Ann Diagn Pathol. 12:340–343. 2008. View Article : Google Scholar : PubMed/NCBI
34	Giaqinis C, Georgiadou M, Dimakopoulou K, Tsourouflis G, Gatzidou E, Kouraklis G and Theocharis S: Clinical significance of MCM-2, MCM-5 expression in colon cancer: Association with clinicopathological parameters and tumor proliferative capacity. Dig Dis Sci. 54:282–291. 2009. View Article : Google Scholar : PubMed/NCBI
35	Xiao H, Tao Y, Greenblatt J and Roeder RG: A cofactor, TIP30, specifically enhances HIV-1 Tat-activated transcription. Proc Natl Acad Sci USA. 95:2146–2151. 1998. View Article : Google Scholar : PubMed/NCBI
36	Shtivelman E: A link between metastasis and resistance to apoptosis of variant small cell lung carcinoma. Oncogene. 14:2167–2173. 1997. View Article : Google Scholar : PubMed/NCBI