MCM proteins as diagnostic and prognostic tumor markers in the clinical setting

Histology and Histopathology

Volumn 25, Issue 3, 2010, Pages 351-370

  Giaginis, Constantinos ^a   Vgenopoulou, Stephanie ^a   Vielh, Philippe ^b   Theocharis, Stamatios ^a  

^a UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^b INSTITUT GUSTAVE ROUSSY   (France)

Author keywords

Cancer; Cell proliferation; Diagnosis; MCM proteins; Prognosis

Indexed keywords

CELL CYCLE PROTEIN; TUMOR MARKER;

CELL PROLIFERATION; HUMAN; METABOLISM; NEOPLASM; PROGNOSIS; REVIEW;

CELL CYCLE PROTEINS; CELL PROLIFERATION; HUMANS; NEOPLASMS; PROGNOSIS; TUMOR MARKERS, BIOLOGICAL;

EID: 77749286992     PISSN: 02133911     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (101)

1. Ayaru L., Stoeber K., Webster G.J., Hatfield A.R., Wollenschlaeger A., Okoturo O., Rashid M., Williams G. and Pereira S.P. (2008). Diagnosis of pancreaticobiliary malignancy by detection of minichromosome maintenance protein 5 in bile aspirates. Br. J. Cancer 98, 1548-1554.
2. Ananthanarayanan V., Pins M.R., Meyer R.E. and Gann P.H. (2005). Immunohistochemical assays in prostatic biopsies processed in Bouin's fixative. J. Clin. Pathol. 58, 322-324.
3. Ananthanarayanan V., Deaton R.J., Yang X.J., Pins M.R. and Gann P.H. (2006). Alteration of proliferation and apoptotic markers in normal and premalignant tissue associated with prostate cancer. BMC Cancer 6, 73.
4. Baldwin P., Laskey R. and Coleman N. (2003). Translational approaches to improving cervical screening. Nat. Rev. Cancer 3, 217-226.
5. Bainsh H. and Gerdes J. (1987). Simultaneous staining of exponentially growing versus plateau phase cells with the proliferation-associated antibody Ki67 and propidium iodide: analysis by flow cytometry. Cell Tissue Kinet. 20, 387-391.
6. Bell S.P. and Dutta A. (2002). DNA replication in eukaryotic cells. Annu. Rev. Biochem. 71, 333-374.
7. Boyd A.S., Shakhtour B. and Shyr Y. (2008). Minichromosome maintenance protein expression in benign nevi, dysplastic nevi, melanoma, and cutaneous melanoma metastases. J. Am. Acad. Dermatol. 58, 750-754.
8. Brown D.C. and Gatter K.C. (2002). Ki67 protein: the immaculate deception? Histopathology 40, 2-11.
9. Burger M., Denzinger S., Hartmann A., Wieland W.F., Stoehr R. and Obermann E.C. (2007). Mcm2 predicts recurrence hazard in stage Ta/T1 bladder cancer more accurately than CK20, Ki67 and histological grade. Br. J. Cancer 96, 1711-5171.
10. Chang V.K., Fitch M.J., Donato J.J., Christensen T.W., Merchant A.M. and Tye B.K. (2003). Mcm1 binds replication origins. J. Biol. Chem. 278, 6093-6100.
11. Chang V.K., Donato J.J., Chan C.S. and Tye B.K. (2004). Mcm1 promotes replication initiation by binding specific elements at replication origins. Mol. Cell. Biol. 24, 6514-6524.
12. Chatrath P., Scott I.S., Morris L.S., Davies R.J., Rushbrook S.M., Bird K., Vowler S.L., Grant J.W., Saeed I.T., Howard D., Laskey R.A. and Coleman N. (2003). Aberrant expression of minichromosome maintenance protein-2 and Ki67 in laryngeal squamous epitheliallesions. Br. J. Cancer 89, 1048-1054.
13. Chatrath P., Scott I.S., Morris L.S., Davies R.J., Bird K., Vowler S.L. and Coleman N. (2006). Immunohistochemical estimation of cell cycle phase in laryngeal neoplasia. Br. J. Cancer 95, 314-321.
14. Cho M.K., Eimoto T., Nagaya S. and Tateyama H. (2006). Cell proliferation marker MCM2, but not Ki67, is helpful for distinguishing between minimally invasive follicular carcinoma and follicular adenoma of the thyroid. Histopathology 48, 801-807.
15. Davies R.J., Freeman A., Morris L.S., Bingham S., Dilworth S., Scott I., Laskey R.A., Miller R and Coleman N. (2002). Analysis of minichromosome maintenance proteins as a novel method for detection of colorectal cancer in stool. Lancet 359, 1917-1919.
16. Davies R.J., Scott I.S., Morris L.S., Rushbrook S.M., Bird K., Vowler S.L., Arends M., Miller R. and Coleman N. (2004). Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease. Colorectal Dis. 6, 103-110.
17. Davidson E.J., Morris L.S., Scott I.S., Rushbrook S.M., Bird K., Laskey R.A., Wilson G.E., Kitchner H.C., Coleman N. and Stern P.L. (2003). Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia. Br. J. Cancer 88:257-262.
18. Dudderidge T.J., Stoeber K., Loddo M., Atkinson G., Fanshawe T., Griffiths D.F., and Williams G.H. (2005). Mcm2, Geminin, and Ki67 define proliferative state and are prognostic markers in renal cell carcinoma. Clin. Cancer Res. 11, 2510-2517.
19. Dudderidge T.J., McCracken S.R., Loddo M., Fanshawe T.R., Kelly J.D., Neal D.E., Leung H.Y., Williams G.H. and Stoeber K. (2007). Mitogenic growth signalling, DNA replication licensing, and survival are linked in prostate cancer. Br. J. Cancer 96, 1384-1393.
20. Endl E., Kausch I., Baack M., Knippers R., Gerdes J. and Scholzen T. (2001). The expression of Ki-67, MCM3, and p27 defines distinct subsets of proliferating, resting, and differentiated cells. J. Pathol. 195, 457-462.
21. Facoetti A., Ranza E., Grecchi I., Benericetti E., Ceroni M., Morbini P. and Nano R. (2006a). Immunohistochemical evaluation of minichromosome maintenance protein 7 in astrocytoma grading. Anticancer Res. 26, 3513-3516.
22. Facoetti A., Ranza E., Benericetti E., Ceroni M., Tedeschi F., Nano R. (2006b). Minichromosome maintenance protein 7: a reliable tool for glioblastoma proliferation index. Anticancer Res. 26, 1071-1075.
23. Freeman A., Morris L.S., Mills A.D., Stoeber K., Laskey R.A., Williams G.H. and Coleman N. (1999). Minichromosome maintenance proteins as biological markers of dysplasia and malignancy. Clin. Cancer Res. 5, 2121-2132.
24. Freeman A., Hamid S., Morris L., Vowler S., Rushbrook S., Wight D.G., Coleman N. and Alexander G.J. (2003). Improved detection of hepatocyte proliferation using antibody to the pre-replication complex: an association with hepatic fibrosis and viral replication in chronic hepatitis C virus infection. J. Viral Hepat. 10, 345-350.
25. Gakiopoulou H., Korkolopoulou P., Levidou G., Thymara I., Saetta A., Piperi C., Givalos N., Vassilopoulos I., Ventouri K., Tsenga A., Bamias A., Dimopoulos M.A., Agapitos E. and Patsouris E. (2007). Minichromosome maintenance proteins 2 and 5 in non-benign epithelial ovarian tumours: relationship with cell cycle regulators and prognostic implications. Br. J. Cancer 97, 1124-1134.
26. Gambichler T., Bischoff S., Bechara F.G., Altmeyer P. and Kreuter A. (2008). Expression of proliferation markers and cell cycle regulators in T cell lymphoproliferative skin disorders. J. Dermatol. Sci. 49, 125-132.
27. Giaginis C., Georgiadou M., Dimakopoulou K., Tsourouflis G., Gatzidou E., Kouraklis G. and Theocharis S. (2009). Clinical significance of MCM-2 and MCM-5 expression in colon cancer: Association with clinicopathological parameters and tumor proliferative capacity. Dig. Dis. Sci. 54, 282-291.
28. Going J.J., Keith W.N., Neilson L., Stoeber K., Stuart R.C. and Williams G.H. (2002). Aberrant expression of minichromosome maintenance proteins 2 and 5, and Ki-67 in dysplastic squamous oesophageal epithelium and Barrett's mucosa. Gut 50, 373-377.
29. Gonzalez M.A., Pinder S.E., Callagy G., Vowler S.L., Morris L.S., Bird K., Bell J.A., Laskey R.A. and Coleman N. (2003). Minichromosome maintenance protein 2 is a strong independent prognostic marker in breast cancer. J. Clin. Oncol. 21, 4306-4313.
30. Gray D., Obermann E.C., Evans M., Hartmann A., Cooper K. and Blaszyk H. (2006). MIB-1 and MCM-2 immunohistochemical analysis does not aid in identification of serrated colorectal polyps with abnormal proliferation. Am. J. Clin. Pathol. 125, 407-412.
31. Guida T., Salvatore G., Faviana P., Ginnini R., Garcia-Rostan G., Provitera L., Basolo F., Fusco A., Carlomagno F. and Santoro M. (2005). Mitogenic effects of the up-regulation of minichromosome maintenance proteins in anaplastic thyroid carcinoma. J. Clin. Endocrinol. Metab. 90, 4703-4709.
32. Guzinska-Ustymowicz K., Stepien E. and Kemona A. (2008). MCM-2, Ki-67 and PCNA protein expressions in pT3G2 colorectal cancer indicated lymph node involvement. Anticancer Res. 28, 451-457.
33. Ha S.A., Shin S.M., Namkoong H., Lee H., Cho G.W., Hur S.Y., Kim T.E. and Kim J.W. (2004). Cancer-associated expression of minichromosome maintenance 3 gene in several human cancers and its involvement in tumorigenesis. Clin. Cancer Res. 10, 8386-8395.
34. Hashimoto K., Araki K., Osaki M., Nakamura H., Tomita K., Shimizu E. and Ito H. (2004). MCM2 and Ki-67 expression in human lung adenocarcinoma: prognostic implications. Pathobiology 71, 193-200.
35. Helfenstein A., Frahm S.O., Krams M., Drescher W., Parwaresch R. and Hassenpflug J. (2004). Minichromosome maintenance protein (MCM6) in low-grade chondrosarcoma: distinction from enchondroma and identification of progressive tumors. Am. J. Clin. Pathol. 122, 912-918.
36. Hiraiwa A., Fujita M., Adachi A., Ono H., Nagasaka T., Matsumoto Y., Ohashi M., Tomita Y. and Ishibashi M. (1998). Specific distribution patterns of hCDC47 expression in cutaneous diseases. J. Cutan. Pathol. 25, 285-290.
37. Huang H.Y., Huang W.W., Lin C.N., Eng H.L., Li S.H., Li C.F., Lu D., Yu S.C. and Hsiung C.Y. (2006). Immunohistochemical expression of p16INK4A, Ki-67, and Mcm2 proteins in gastrointestinal stromal tumors: prognostic implications and correlations with risk stratification of NIH consensus criteria. Ann. Surg. Oncol. 13, 1633-1644.
38. Huang X.P., Rong T.H., Wu Q.L., Fu J.H., Yang H., Zhao J.M. and Fang Y. (2005). MCM4 expression in esophageal cancer from southern China and its clinical significance. J. Cancer Res. Clin. Oncol. 131, 677-682.
39. Hunt D.P., Freeman A., Morris L.S., Burnet N.G., Bird K., Davies T.W., Laskey R.A. and Coleman N. (2002). Early recurrence of benign meningioma correlates with expression of mini-chromosome maintenance-2 protein. Br. J. Neurosurg. 16, 10-15.
40. Ishimi Y., Okayasu I., Kato C., Kwon H.J., Kimura H., Yamada K. and Song S.Y. (2003). Enhanced expression of Mcm proteins in cancer cells derived from uterine cervix. Eur. J. Biochem. 270, 1089-1101.
41. Kato H., Miyazaki T., Fukai Y., Nakajima M., Sohda M., Takita J., Masuda N., Fukuchi M., Manda R., Ojima H., Tsukada K., Asao T. and Kuwano H. (2003a). A new proliferation marker, minichromosome maintenance 2, is associated with tumor aggressiveness in esophageal squamous cell carcinoma. J. Surg. Oncol. 84, 24-30.
42. Kato K., Toki T., Shimizu M., Shiozawa T., Fujii S., Nikaido T. and Konishi I. (2003b). Expression of replication-licensing factors MCM2 and MCM3 in normal, hyperplastic, and carcinomatous endometrium: correlation with expression of Ki-67 and estrogen and progesterone receptors. Int. J .Gynecol. Pathol. 22, 334-340.
43. Kebebew E., Peng M., Reiff E., Duh Q-Y., Clark O.H. and McMillan A. (2006). Diagnostic and prognostic value of cell-cycle regulatory genes in malignant thyroid neoplasms. World J. Surg. 30, 767-774.
44. Kodani I., Shomori K., Osaki M., Kuratate I., Ryoke K. and Ito H. (2001). Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasiacarcinoma sequence of the oral mucosa. Pathobiology 69, 150-158.
45. Kodani I., Osaki M., Shomori K., Araki K., Goto E., Ryoke K. and Ito H. (2003). Minichromosome maintenance 2 expression is correlated with mode of invasion and prognosis in oral squamous cell carcinomas. J. Oral Pathol. Med. 32, 468-474.
46. Korkolopoulou P., Givalos N., Saetta A., Goudopoulou A., Gakiopoulou H., Thymara I., Thomas-Tsagli E. and Patsouris E. (2005). Minichromosome maintenance proteins 2 and 5 expression in muscle-invasive urothelial cancer: a multivariate survival study including proliferation markers and cell cycle regulators. Hum. Pathol. 36, 899-907.
47. Krüger S., Thorns C., Stöcker W., Müller-Kunert E., Böhle A. and Feller A.C. (2003). Prognostic value of MCM2 immunoreactivity in stage T1 transitional cell carcinoma of the bladder. Eur. Urol. 43, 138-145.
48. Laitinen S., Martikainen P.M., Tolonen T., Isola J., Tammela T.L. and Visakorpi T. (2008). EZH2, Ki-67 and MCM7 are prognostic markers in prostatectomy treated patients. Int. J. Cancer 122, 595-602.
49. Lampert I.A., Horncastle D., Dilworth S., Roberts I., Alison M.R. and Naresh K.N. (2005). The expression of minichromosome maintenance protein-2 in normal and abnormal megakaryocytes and comparison with the proliferative marker Ki-67. Br. J. Haematol. 131, 490-494.
50. Laskey R.A. and Madine M.A. (2003). A rotary pumping model for helicase function of MCM proteins at a distance from replication forks. EMBO Rep. 4, 26-30.
51. Li S.S., Xue W.C., Khoo U.S., Ngan H.Y., Chan K.Y., Tam I.Y., Chiu P.M., Ip P.P., Tam KF. and Cheung A.N. (2005). Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis. Histopathology 46, 307-313.
52. Liu H., Takeuchi S., Moroi Y., Lin N., Urabe K., Kokuba H., Imafuku S., Dainichi T., Uchi H., Furue M. and Tu Y. (2007). Expression of minichromosome maintenance 5 protein in proliferative and malignant skin diseases. Int. J. Dermatol. 46, 1171-1176.
53. Lutzmann M., Maiorano D. and Mechali M. (2005). Identification of full genes and proteins of MCM9, a novel, vertebrate-specific member of the MCM2-8 protein family. Gene 362, 51-56.
54. MacCallum D.E. and Hall P.A. (2000). The location of pKi67 in the outer dense fibrillary compartment of the nucleolus points to a role in ribosome biogenesis during the cell division cycle. J. Pathol. 190, 537-544.
55. Maiorano D., Cuvier O., Danis E. and Mechali M. (2005). MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiation. Cell 120, 315-328.
56. Maiorano D., Lutzmann M. and Merchali M. (2006). MCM proteins and DNA replication. Curr. Opin. Cell. Biol. 18, 130-136.
57. Marshall A., Rushbrook S., Davies S.E., Morris L.S., Scott I.S., Vowler S.L., Coleman N. and Alexander G. (2005a). Relation between hepatocyte G1 arrest, impaired hepatic regeneration, and fibrosis in chronic hepatitis C virus infection. Gastroenterology 128, 33-42. (Pubitemid 40039956)
58. Marshall A., Rushbrook S., Morris L.S., Scott I.S., Vowler S.L., Favies S.E., Coleman N. and Alexander G. (2005b). Hepatocyte expression of minichromosome maintenance protein-2 predicts fibrosis progression after transplantation for chronic hepatitis C virus: a pilot study. Liver Transpl. 11, 427-433.
59. Matsubara T., Eimoto T., Okabe M., Miyabe S., Fujiyoshi Y., Matsushita Y., Mizutani J., Yamada S. and Otsuka T. (2008). Proliferation and apoptosis of tumour cells before and after neoadjuvant therapy for high-grade extremity sarcomas: divergent associations with tumour response and prognosis. Histopathology 52, 706-716.
60. Mehrotra P., Gonzalez M.A., Johnson S.J., Coleman N., Wilson J.A., Davies B.R., and Lennard T.W.J. (2006). Mcm-2 and Ki-67 have limited potential in preoperative diagnosis of thyroid malignancy. Laryngoscope 116, 1434-1438.
61. Meng M.V., Grossfeld G.D., Williams G.H., Dilworth S., Stoeber K., Mulley T.W., Weinberg V., Carroll P.R. and Tlsty T.D. (2001). Minichromosome maintenance protein 2 expression in prostate: characterization and association with outcome after therapy for cancer. Clin. Cancer Res. 7, 2712-2718.
62. Mukherjee G., Muralidhar B., Bafna U.D., Laskey R.A. and Coleman N. (2007). MCM immunocytochemistry as a first line cervical screening test in developing countries: a prospective cohort study in a regional cancer centre in India. Br. J. Cancer 96, 1107-1111.
63. Murphy N., Ring M., Heffron C.C., King B., Killalea A.G., Hughes C., Martin C.M., McGuinness E., Sheils O. and O' Leary J.J. (2005). p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasia and cervical cancer. J. Clin. Pathol. 58, 525-534.
64. Niklaus A.L., Aubuchon M., Zapantis G., Li P., Quian H., Isaac B., Kim M.Y., Adel G., Pollard J.W. and Santoro N.F. (2007). Assessment of the proliferative status of epithelial cell types in the endometrium of young and menopausal transition women. Hum. Reprod. 22, 1778-1788.
65. Obermann E.C., Went P., Zimpfer A., Tzankov A., Wild P.J., Stoehr R., Pileri S.A. and Dimhofer S. (2005). Expression of minichromosome maintenance protein 2 as a marker for proliferation and prognosis in diffuse large B-cell lymphoma: a tissue microarray and clinicopathological analysis. BMC Cancer 5, 162.
66. Obermann E.C., Went P., Tzankov A., Pileri S.A., Hofstaedter F., marienhagen J., Stoehr R. and Dirnhofer S. (2007). Cell cycle phase distribution analysis in chronic lymphocytic leukaemia: a significant number of cells reside in early G1-phase. J. Clin. Pathol. 60, 794-797.
67. Osaki M., Osaki M., Yamashita H., Shomori K., Yoshida H. and Ito H. (2002). Expression of minichromosome maintenance-2 in human malignant fibrous histiocytomas: Correlations with Ki-67 and P53 expression, and apoptosis. Int. J. Mol. Med. 10, 161-168.
68. Padmanabhan V., Callas P., Philips G., Trainer T.D. and Beatty B.G. (2004). DNA replication regulation protein Mcm7 as a marker ofproliferation in prostate cancer. J. Clin. Pathol. 57, 1057-1062.
69. Quaglia A., McStay M., Stoeber K., Loddo M., Caplin M., Fanshawe T., Williams G. and Dhillon A. (2006). Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma. Liver Int. 26, 424-432.
70. Ramnath N., Hernandez F.J., Tan D.F., Huberman J.A., Beck A.F., Hyland A., Todorov I.T., Brooks J.S. and Bepler G. (2001). MCM2 is an independent predictor of survival in patients with non-small-cell lung cancer. J. Clin. Oncol. 19, 4259-4266.
71. Ricke R.M. and Bielinsky A.K. (2004). Mcm10 regulates the stability and chromatin association of DNA polymerase-α. Mol. Cell. 16, 173-185.
72. Rodins K., Cheale M., Coleman N. and Fox S.B. (2002). Minichromosome maintenance protein 2 expression in normal kidney and renal cell carcinomas: Relationship to tumor dormancy and potential clinical utility. Clin. Cancer Res. 8, 1075-1081.
73. Romanowski P. and Madine M.A.. (1997). Mechanisms restricting DNA replication to once per cell cycle: the role of Cdc6 and ORC. Trends Cell. Biol. 7, 9-10.
74. Schrader C., Janssen D., Klapper W., Siebmann J.U., Meusers P., Britinger G., Kneba M., Tiemann M. and Parwaresch R. (2005). Minichromosome maintenance protein 6, a proliferation marker superior to Ki-67 and independent predictor of survival in patients with mantle cell lymphoma. Br. J. Cancer 93, 939-945.
75. Scott I.S., Morris L.S., Bird K., Davies R.J., Vowler S.L, Rushbrook S.M., Marshall A.E., Laskey R.A., Miller R., Arends M.J. and Coleman N. (2003). A novel immunohistochemical method to estimate cell-cycle phase distribution in archival tissue: implications for the prediction of outcome in colorectal cancer. J. Pathol. 201, 187-197.
76. Scott I.S., Heath T.M., Morris L.S., Rushbrook S.M., Bird K., Vowler S.L., Arends M.J. and Coleman N. (2004). A novel immunohistochemical method for estimating cell cycle phase distribution in ovarian serous neoplasms: implications for the histopathological assessment of paraffin-embedded specimens. Br. J. Cancer 90, 1583-1590.
77. Scott I.S., Morris L.S., Rushbrook S.M., Bird K., Vowler S.L., Burnet N.G. and Coleman N. (2005). Immunohistochemical estimation of cell cycle entry and phase distribution in astrocytomas: applications in diagnostic neuropathology. Neuropathol. Appl. Neurobiol. 31, 455-466.
78. Scott I.S., Odell E., Chatrath P., Morris L.S., Davies R.J., Vowler S.L., Laskey R.A. and Coleman N. (2006). A minimally invasive immunocytochemical approach to early detection of oral squamous cell carcinoma and dysplasia. Br. J. Cancer 94, 1170-1175.
79. Sington J.D., Morris L.S., Nicholson A.G. and Coleman N. (2003). Assessment of cell cycle state may facilitate the histopathological diagnosis of malignant mesothelioma. Histopathology 42, 498-502.
80. Sington J.D., Freeman A., Morris L.S., Vowler S.L., Arch B.N. and Fisher C. (2004). Minichromosome maintenance protein in myxofibrosarcoma. Mod. Pathol. 17, 235-240.
81. Sirieix P.S., O'Donovan M., Brown J., Save V., Coleman N. and Fitzgerald R.C. (2003). 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.
82. Söling A., Sackewitz M., Volkmar M., Schaarschmidt D., Jacob R., Holzhausen H.J. and Rainov N.G. (2005). Minichromosome maintenance protein 3 elicits a cancer-restricted immune response in patients with brain malignancies and is a strong independent predictor of survival in patients with anaplastic astrocytoma. Clin. Cancer Res. 11, 249-258.
83. Szelachowska J., Dziegiel P., Jelen-Krzeszewska J., Jelen M., Matkowski R., Pomiencko A., Spytkowska B., Jagas M., Gisterek I. and Kornafel J. (2006). Mcm-2 protein expression predicts prognosis better than Ki-67 antigen in oral cavity squamocellular carcinoma. Anticancer Res. 26, 2473-2478.
84. Shetty A., Loddo M., Fanshawe T., Prevost A.T., Sainsbury R., Williams G.H. and Stoeber K. (2005). DNA replication licensing and cell cycle kinetics of normal and neoplastic breast. Br. J. Cancer 93, 1295-300.
85. Shima N., Buske T.R. and Schimenti J.C. (2007). Genetic screen for chromosome instability in mice: Mcm4 and breast cancer. Cell Cycle 6, 1135-1140. (Pubitemid 47327976)
86. Stoeber K., Swinn R., Prevost A.T., de Clive-Lowe P., Halsall I., Dilwort S.M., Marr J., Turner W.H., Bullock N., Doble A., Hales C.N. and Williams G.H. (2002). Diagnosis of genito-urinary tract cancer by detection of minichromosome maintenance 5 protein in urine sediments. J. Natl. Cancer Inst. 94, 1071-1079.
87. Tachibana K.K., Gonzalez M.A. and Coleman N. (2005). Cell-cycledependent regulation of DNA replication and its relevance to cancer pathology. J. Pathol. 205, 123-129.
88. Takisawa H., Mimura S. and Kubota Y. (2000). Eukaryotic DNA replication: from-replication complex to initiation complex. Curr. Opin. Cell. Biol. 12, 690-696.
89. Tan D.F., Huberman J.A., Hyland A., Loewen G.M., Brooks J.S., Beck A.F., Todorov I.T. and Bepler G. (2001). MCM2-a promising marker for premalignant lesions of the lung: a cohort study. BMC Cancer 1, 6.
90. Tye B.K. (1999). MCM proteins in DNA replication. Annu. Rev. Biochem. 68, 649-686.
91. Theocharis S.E., Skopelitou A.S., Margeli A.P., Pavlaki K.J. and Kittas C. (1994). Proliferating cell nuclear antigen (PCNA) expression in regenerating rat liver after partial hepatectomy. Dig. Dis. Sci. 39, 245-252. (Pubitemid 24073596)
92. Tokuyasu N., Shomori K., Nishihara K., Kawaguchi H., Fujioka S., Yamaga K., Ikeguchi M. and Ito H. (2008). Minichromosome maintenance 2 (MCM2) immunoreactivity in stage III human gastric carcinoma: clinicopathological significance. Gastric Cancer 11, 37-46.
93. Toshi L. and Bravo R. (1988). Changes in cyclin/proliferating cell nuclear antigen distribution during DNA repair synthesis. J. Cell. Biol. 107, 1623-1628.
94. Vargas P.A., Cheng Y., Barrett A.W., Craig G.T. and Speight P.M. (2008). Expression of Mcm-2, Ki-67 and geminin in benign and malignant salivary gland tumours. J. Oral Pathol. Med. 37, 309-318.
95. Yang J., Ramnath N., Moysich K.B., Asch H.L., Swede H., Alrawi S.J., Huberman J., Geradts J., Brooks J.S. and Tan D. (2006). Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer. BMC Cancer 6, 203.
96. Wei Q., Li Y., Chen L., Zhang L., He X., Fu X., Ying K., Huang J., Chen Q., Xie Y. and Mao Y. (2006). Genes differentially expressed in responsive and refractory acute leukemia. Front. Biosci. 11, 977-982.
97. Williams G.H., Romanowski P., Morris L., Madine M., Mills A.D., Stoeber K., Marr J., Laskey R.A. and Coleman N. (1998). Improvedcervical smear assessment using antibodies against proteins that regulate DNA replication. Prco. Natl. Acad. Sci. USA 5, 14932-14937.
98. Williams G.H., Swinn R., Prevost A.T., De Clive-Lowe P., Halsall I., Going J.J., Hales C.N., Stoeber K. and Middleton S.J. (2004). Diagnosis of oesophageal cancer by detection of minichromosome maintenance 5 protein in gastric aspirates. Br. J. Cancer 91, 714-719.
99. Wharton S.B., Chan K.K., Anderson J.R., Stoeber K. and Williams C.H. (2001). Replicative Mcm2 protein as a novel proliferation marker in oligodendrogliomas and its relationship to Ki-67 labeling index, histological grade and prognosis. Nephropathol. Appl. Neurobiol. 27, 305-313.
100. Xu J., Zhang S., You C., Huang S., Cai B. and Wang X. (2007). Expression of human MCM6 and DNA Topo II alpha in craniopharyngiomas and its correlation with recurrence of the tumor. J. Neurooncol. 83, 183-189.
101. Winnepenninckx V., Lazar V., Michiels S., Dessen P., Stas M., Alonso S.R., Avril M.F., Ortiz Romero P.L., Robert T., Balacescu O., Eggermont A.M., Lenoir G., Sarasin A., Tursz T., van den Oord J.J., Spatz A. and Melanoma Group of the European Organization for Research and Treatment of Cancer. (2006). Gene expression profiling of primary cutaneous melanoma and clinical outcome, J. Natl. Cancer Inst. 98, 472-482.