Discussion/Conclusion

Cancer biomarkers offer a great potential for improving the management of cancer at every point from screening and detection, diagnosis, staging, prognosis, and assessment of treatment response.20 Biomarkers offer the hope of early detection as well as tracking cancer progression and recurrence.66

Early detection may help improve survival of HIV-positive cancer patients, as it could help identify HIV-positive individuals at most risk of cancer development distinguish aggressive from indolent malignancies and track disease progression.


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Discovery of new biomarkers suitable for clinical application may aid the diagnosis and classification of cancer, which in turn, should lead to better patient stratification.140 Biomarkers do not need to be cancer specific to be useful; certain proteins may help predict response to therapy or aid in the monitoring of disease progression.141

As cancer is increasingly defined by dysregulated pathways, relevant biomarkers may cut across tumor types without showing tissue specificity. Abundance of potential cancer biomarkers have been discovered, however, only few of them have been integrated into clinical practice.

This is due to the fact that some of these biomarkers are not highly sensitive and specific for cancer detection. It is well recognized that the road from biomarker discovery, validation, and regulatory approval to the translation into clinical setting could be long and difficult.11

A new era is underway in which cancer detection, diagnosis, and treatment will be guided increasingly by the molecular attributes of the individual patient.142 The future of cancer therapy lies in the use of biomarkers that offer the potential to identify and treat cancer years before it is either visible or symptomatic.

In addition, the future of cancer management is expected to be profoundly dependent upon the use of biomarkers that will guide physicians at every step of disease management.143 Cancer biomarkers can be used for the accurate evaluation and management of the disease.

Author Contributions

Conceived and designed the experiments: BF, GS, PB, BR. Analyzed the data: BF, GS, PB, BR. Wrote the first draft of the manuscript: BF. Contributed to the writing of the manuscript: BF, GS, PB, BR. Agree with manuscript results and conclusions: BF, GS, PB, BR. Jointly developed the structure and arguments for the paper: BF, GS, PB, BR. Made critical revisions and approved final version: BF, GS, PB, BR. All authors reviewed and approved of the final manuscript.

References

  1. Diamandis M, White NM, Yousef GM. Personalized medicine: marking a new epoch in cancer patient management. Mol Cancer Res. 2010;8(9):1175–1187. [PubMed]
  2. Sasco AJ, Jaquet A, Boidin E, et al. The challenge of AIDS-related malignancies in sub-Saharan Africa.PLoS One. 2010;5(1):e8621. [PMC free article] [PubMed]
  3. Casper C. The increasing burden of HIV-associated malignancies in resource-limited regions. Annu Rev Med. 2011;62:157–170. [PubMed]
  4. Ambinder RF, Bhatia K, Martinez-Maza O, Mitsuyasu R. Cancer biomarkers in HIV patients. Curr Opin HIV AIDS. 2010;5(6):531–537. [PMC free article] [PubMed]
  5. McDonald KL. In: Biomarker Discovery, Validation and Clinical Application for Patients Diagnosed with Glioma, Glioma—Exploring Its Biology and Practical Relevance. Ghosh Anirban., editor. InTech; 2011. [Accessed September 1, 2014]. Available at http://www.intechopen.com/books/glioma-exploring-its-biology-andpractical-relevance/biomarker-discovery-validation-and-clinical-application-for-patients-diagnosed-with-glioma.
  6. Verma M. Personalized medicine and cancer. J Pers Med. 2012;2(1):1–14.
  7. Park JW, Kerbel RS, Kelloff GJ, et al. Rationale for biomarkers and surrogate end points in mechanism-driven oncology drug development. Clin Cancer Res. 2004;10(11):3885–3896. [PubMed]
  8. Biomarkers Definitions Working Group Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95. [PubMed]
  9. Lesko LJ, Atkinson AJ., Jr Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol. 2001;41:347–366.[PubMed]
  10. Malati T. Tumour markers: an overview. Indian J Clin Biochem. 2007;22(2):17–31. [PMC free article][PubMed]
  11. Füzéry AK, Levin J, Chan MM, Chan DW. Translation of proteomic biomarkers into FDA approved cancer diagnostics: issues and challenges. Clin Proteomics. 2013;10(1):13. [PMC free article] [PubMed]
  12. Srinivas PR, Kramer BS, Srivastava S. Trends in biomarker research for cancer detection. Lancet Oncol.2001;2(11):698–704. [PubMed]
  13. Verma M, Manne U. Genetic and epigenetic biomarkers in cancer diagnosis and identifying high risk populations. Crit Rev Oncol Hematol. 2006;60(1):9–18. [PubMed]
  14. Miaskowski C, Aouizerat BE. Biomarkers: symptoms, survivorship, and quality of life. Semin Oncol Nurs. 2012;28(2):129–138. [PMC free article] [PubMed]
  15. Overdevest JB, Theodorescu D, Lee JK. Utilizing the molecular gateway: the path to personalized cancer management. Clin Chem. 2009;55(4):684–697. [PubMed]
  16. Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov.2003;2(7):566–580. [PubMed]
  17. Etzioni R, Urban N, Ramsey S, et al. The case for early detection. Nat Rev Cancer. 2003;3(4):243–252.[PubMed]
  18. Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer. 2005;5(11):845–856. [PubMed]
  19. Heckman-Stoddard BM. Oncology biomarkers: discovery, validation, and clinical use. Semin Oncol Nurs. 2012;28(2):93–98. [PubMed]
  20. Mishra A, Verma M. Cancer biomarkers: are we ready for the prime time? Cancers. 2010;2(1):190–208.[PMC free article] [PubMed]
  21. Pereira PF, Cuzzi T, Galhardo MC. Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators.An Bras Dermatol. 2013;88(2):243–246. [PMC free article] [PubMed]
  22. Pantanowitz L, Dezube BJ, Pinkus GS, Tahan SR. Histological characterization of regression in acquired immunodeficiency syndrome-related Kaposi’s sarcoma. J Cutan Pathol. 2004;31(1):26–34. [PubMed]
  23. Groopman JE. AIDS-Related Kaposi Sarcoma: Staging and Treatment. UpToDate. 2013. [Accessed January 6, 2014]. Available at http://www.uptodate.com/contents/aids-related-kaposi-sarcoma-staging-and-treatment?source=search_result&search=Biomarkers+in+Kaposi+Sarcoma&selectedTitle=2~150.
  24. Nagata N, Igari T, Shimbo T, et al. Diagnostic value of endothelial markers and HHV-8 staining in gastrointestinal Kaposi sarcoma and its difference in endoscopic tumor staging. World J Gastroenterol.2013;19(23):3608–3614. [PMC free article] [PubMed]
  25. Cheuk W, Wong KO, Wong CS, Dinkel JE, Ben-Dor D, Chan JK. Immunostaining for human herpesvirus 8 latent nuclear antigen-1 helps distinguish Kaposi sarcoma from its mimickers. Am J Clin Pathol. 2004;121(3):335–342. [PubMed]
  26. Patel RM, Goldblum JR, Hsi ED. Immunohistochemical detection of human herpes virus-8 latent nuclear antigen-1 is useful in the diagnosis of Kaposi sarcoma. Mod Pathol. 2004;17(4):456–460. [PubMed]
  27. Horenstein MG, Cesarman E, Wang X, Linkov I, Prieto VG, Louie DC. Cyclin D1 and retinoblastoma protein expression in Kaposi’s sarcoma. J Cutan Pathol. 1997;24(10):585–589. [PubMed]
  28. Hong A, Davies S, Stevens G, Lee CS. Cyclin D1 overexpression in AIDS-related and classic Kaposi sarcoma. Appl Immunohistochem Mol Morphol. 2004;12(1):26–30. [PubMed]
  29. Long E, Ilie M, Hofman V, et al. LANA-1, Bcl-2, Mcl-1 and HIF-1alpha protein expression in HIV-associated Kaposi sarcoma. Virchows Arch. 2009;55(2):159–170. [PubMed]
  30. Pantanowitz L, Schwartz EJ, Dezube BJ, Kohler S, Dorfman RF, Tahan SR. C-Kit (CD117) expression in AIDS-related, classic, and African endemic Kaposi sarcoma. Appl Immunohistochem Mol Morphol.2005;13(2):162–166. [PubMed]
  31. Moses AV, Jarvis MA, Raggo C, et al. Kaposi’s sarcoma-associated herpesvirus-induced upregulation of the c-kit proto-oncogene, as identified by gene expression profiling, is essential for the transformation of endothelial cells. J Virol. 2002;76(16):8383–8399. [PMC free article] [PubMed]
  32. Schwartz EJ, Dorfman RF, Kohler S. Human herpesvirus-8 latent nuclear antigen-1 expression in endemic Kaposi sarcoma: an immunohistochemical study of 16 cases. Am J Surg Pathol. 2003;27(12):1546–1550. [PubMed]
  33. Pulitzer M. Molecular diagnosis of infection-related cancers in dermatopathology. Semin Cutan Med Surg. 2012;31(4):247–257. [PubMed]
  34. Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR. Kaposi’s sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells. Proc Natl Acad Sci U S A.2005;102(15):5570–5575. [PMC free article] [PubMed]
  35. Ojala PM, Tiainen M, Salven P, et al. Kaposi’s sarcoma-associated herpesvirus-encoded v-cyclin triggers apoptosis in cells with high levels of cyclin-dependent kinase 6. Cancer Res. 1999;59(19):4984–4989.[PubMed]
  36. Friborg J, Jr, Kong W, Hottiger MO, Nabel GJ. p53 inhibition by the LANA protein of KSHV protects against cell death. Nature. 1999;402(6764):889–894. [PubMed]
  37. Si H, Robertson ES. Kaposi’s sarcoma-associated herpesvirus-encoded latency-associated nuclear antigen induces chromosomal instability through inhibition of p53 function. J Virol. 2006;80(2):697–709.[PMC free article] [PubMed]
  38. Rosado FG, Itani DM, Coffin CM, Cates JM. Utility of immunohistochemical staining with FLI1, D2-40, CD31, and CD34 in the diagnosis of acquired immunodeficiency syndrome-related and non-acquired immunodeficiency syndrome-related Kaposi sarcoma. Arch Pathol Lab Med. 2012;136(3):301–304.[PubMed]
  39. Arai E, Kuramochi A, Tsuchida T, et al. Usefulness of D2-40 immunohistochemistry for differentiation between kaposiform hemangioendothelioma and tufted angioma. J Cutan Pathol. 2006;33(7):492–497.[PubMed]
  40. Kahn HJ, Bailey D, Marks A. Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi’s sarcoma and a subset of angiosarcomas. Mod Pathol. 2002;15(4):434–440. [PubMed]
  41. Russell Jones R, Orchard G, Zelger B, Wilson Jones E. Immunostaining for CD31 and CD34 in Kaposi sarcoma. J Clin Pathol. 1995;48(11):1011–1016. [PMC free article] [PubMed]
  42. Faris M, Ensoli B, Kokot N, Nel AE. Inflammatory cytokines induce the expression of basic fibroblast growth factor (bFGF) isoforms required for the growth of Kaposi’s sarcoma and endothelial cells through the activation of AP-1 response elements in the bFGF promoter. AIDS. 1998;12(1):19–27. [PubMed]
  43. Kennedy MM, Biddolph S, Lucas SB, et al. Cyclin D1 expression and HHV8 in Kaposi sarcoma. J Clin Pathol. 1999;52(8):569–573. [PMC free article] [PubMed]
  44. Aoki Y, Yarchoan R, Wyvill K, Okamoto S, Little RF, Tosato G. Detection of viral interleukin-6 in Kaposi sarcoma-associated herpesvirus-linked disorders. Blood. 2001;97(7):2173–2176. [PubMed]
  45. Koopal S, Furuhjelm JH, Järviluoma A, et al. Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis. PLoS Pathog. 2007;3(9):1348–1360. [PMC free article][PubMed]
  46. Sakakibara S, Pise-Masison CA, Brady JN, Tosato G. Gene regulation and functional alterations induced by Kaposi’s sarcoma-associated herpesvirus-encoded ORFK13/vFLIP in endothelial cells. J Virol.2009;83(5):2140–2153. [PMC free article] [PubMed]
  47. Ballon G, Chen K, Perez R, Tam W, Cesarman E. Kaposi sarcoma herpesvirus (KSHV) vFLIP oncoprotein induces B cell transdifferentiation and tumorigenesis in mice. J Clin Invest. 2011;121(3):1141–1153. [PMC free article] [PubMed]
  48. Hussain SK, Hessol NA, Levine AM, et al. Serum biomarkers of immune activation and subsequent risk of non-Hodgkin B-cell lymphoma among HIV-infected women. Cancer Epidemiol Biomarkers Prev.2013;22(11):2084–2093. [PMC free article] [PubMed]
  49. Chen X, Cheng L, Jia X, et al. Human immunodeficiency virus type 1 Tat accelerates Kaposi sarcoma-associated herpesvirus Kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice. Neoplasia. 2009;11(12):1272–1284. [PMC free article] [PubMed]
  50. Tappero JW, Conant MA, Wolfe SF, Berger TG. Kaposi’s sarcoma: epidemiology, pathogenesis, histology, clinical spectrum, staging criteria and therapy. J Am Acad Dermatol. 1993;28(3):371–395.[PubMed]
  51. Simonart T, Van Vooren JP. Interleukin-1 beta increases the BCL-2/BAX ratio in Kaposi’s sarcoma cells. Cytokine. 2002;19(6):259–266. [PubMed]
  52. Guo WX, Antakly T, Cadotte M, et al. Expression and cytokine regulation of glucocorticoid receptors in Kaposi’s sarcoma. Am J Pathol. 1996;148(6):1999–2008. [PMC free article] [PubMed]
  53. Cai J, Gill PS, Masood R, et al. Oncostatin-M is an autocrine growth factor in Kaposi’s sarcoma. Am J Pathol. 1994;145(1):74–79. [PMC free article] [PubMed]
  54. Amaral MC, Miles S, Kumar G, Nel AE. Oncostatin-M stimulates tyrosine protein phosphorylation in parallel with the activation of p42MAPK/ERK-2 in Kaposi’s cells. Evidence that this pathway is important in Kaposi cell growth. J Clin Invest. 1993;92(2):848–857. [PMC free article] [PubMed]
  55. American Cancer Society Cancer Facts and Figures 2010. 2010. [Accessed June 11, 2013]. Available athttp://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf.
  56. Shankland KR, Armitage JO, Hancock BW. Non-Hodgkin lymphoma. Lancet. 2012;380(9844):848–857. [PubMed]
  57. Pörtner LM, Schönberg K, Hejazi M, et al. T and NK cells of B cell NHL patients exert cytotoxicity against lymphoma cells following binding of bispecific tetravalent antibody CD19 × CD3 or CD19 × CD16.Cancer Immunol Immunother. 2012;61(10):1869–1875. [PubMed]
  58. Chan JK. The new World Health Organization classification of lymphomas: the past, the present and the future. Hematol Oncol. 2001;19(4):129–150. [PubMed]
  59. BioOncology . Non-Hodgkin’s Lymphoma: A Histopathologic and Prognostic Evaluation. Gentech; USA: 2010. [Accessed November 11, 2013]. Available at http://www.biooncology.com/research-education/bcell/downloads/GA10000083900_NHL_Primer.pdf.
  60. Emmanuel B, Anderson WF. Non-Hodgkin lymphoma in early life. J Natl Cancer Inst.2012;104(12):888–889. [PMC free article] [PubMed]
  61. Chao C, Silverberg MJ, Martínez-Maza O, et al. Epstein-Barr virus infection and expression of B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma. Clin Cancer Res. 2012;18(17):4702–4712.[PMC free article] [PubMed]
  62. Barreto L, Azambuja D, Morais JC. Expression of immunohistochemical markers in patients with AIDS-related lymphoma. Braz J Infect Dis. 2012;16(1):74–77. [PubMed]
  63. Sangle NA, Agarwal AM, Smock KJ, et al. Diffuse large B-cell lymphoma with aberrant expression of the T-cell antigens CD2 and CD7. Appl Immunohistochem Mol Morphol. 2011;19(6):579–583. [PubMed]
  64. Kim MK, Bae SH, Bae YK, et al. Biological characterization of nodal versus extranodal presentation of diffuse large B-cell lymphoma using immunohistochemistry. Clin Lymphoma Myeloma Leuk.2011;11(5):403–408. [PubMed]
  65. De Mello CA, De Andrade VP, De Lima VC, Carvalho AL, Soares FA. Prognostic impact of MUM1 expression by immunohistochemistry on primary mediastinal large B-cell lymphoma. Leuk Lymphoma.2011;52(8):1495–1503. [PubMed]
  66. Dave H, Learn C, Lieberman R. Biomarkers: Recent Advances in Their Application to the Treatment of Hematologic Malignancies. Quintiles; 2013. [Accessed May 1, 2014]. Available athttp://www.quintiles.com/library/white-papers/biomarkers-recent-advances-in-their-application-to-the-treatment-of-hematologic-malignancies.pdf.
  67. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–511. [PubMed]
  68. Nyman H, Adde M, Karjalainen-Lindsberg ML, et al. Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood. 2007;109(11):4930–4935. [PubMed]
  69. Zinzani PL, Dirnhofer S, Sabattini E, et al. Identification of outcome predictors in diffuse large B-cell lymphoma. Immunohistochemical profiling of homogeneously treated de novo tumors with nodal presentation on tissue micro-arrays. Haematologica. 2005;90(3):341–347. [PubMed]
  70. Habara T, Sato Y, Takata K, et al. Germinal center B-cell-like versus non-germinal center B-cell-like as important prognostic factor for localized nodal DLBCL. J Clin Exp Hematop. 2012;52(2):91–99. [PubMed]
  71. Visco C, Li Y, Xu-Monette ZY, et al. Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Leukemia. 2012;26(9):2103–2113. [PMC free article] [PubMed]
  72. Schmitz R, Young RM, Ceribelli M, et al. Burkitt lymphoma pathogenesis and therapeutic targets from structural and functional genomics. Nature. 2012;490(7418):116–120. [PMC free article] [PubMed]
  73. Mead GM, Barrans SL, Qian W, et al. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial) Blood. 2008;112(6):2248–2260. [PMC free article] [PubMed]
  74. Levine AM. Challenges in the management of Burkitt’s lymphoma. Clin Lymphoma. 2002;3(suppl 1):S19–S25. [PubMed]
  75. Armitage JO. How I treat patients with diffuse large B-cell lymphoma. Blood. 2007;110(1):29–36.[PubMed]
  76. Steinfort DP, Conron M, Tsui A, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for the evaluation of suspected lymphoma. J Thorac Oncol. 2010;5(6):804–809. [PubMed]
  77. Kaplan LD. HIV-associated lymphoma. Best Pract Res Clin Haematol. 2012;25(1):101–117. [PubMed]
  78. Freedman AS, Friedberg JW. Evaluation and Staging of Non-Hodgkin Lymphoma. UpToDate. 2013. [Accessed June 1, 2014]. Available at http://www.uptodate.com/contents/evaluation-and-staging-of-non-hodgkin-lymphoma?source=search_result&search=non+hodgkins+lymphoma&selectedTitle=5~150.
  79. Hasselblom S, Ridell B, Sigurdardottir M, Hansson U, Nilsson-Ehle H, Andersson PO. Low rather than high Ki-67 protein expression is an adverse prognostic factor in diffuse large B-cell lymphoma. Leuk Lymphoma. 2008;49(8):1501–1509. [PubMed]
  80. Li ZM, Huang JJ, Xia Y, et al. High Ki-67 expression in diffuse large B-cell lymphoma patients with non-germinal center subtype indicates limited survival benefit from R-CHOP therapy. Eur J Haematol.2012;88(6):510–517. [PubMed]
  81. Dong HY, Browne P, Liu Z, Gangi M. PAX-5 is invariably expressed in B-cell lymphomas without plasma cell differentiation. Histopathology. 2008;53(3):278–287. [PubMed]
  82. Desouki MM, Post GR, Cherry D, Lazarchick J. PAX-5: a valuable immunohistochemical marker in the differential diagnosis of lymphoid neoplasms. Clin Med Res. 2010;8(2):84–88. [PMC free article] [PubMed]
  83. Yu B, Zhou X, Li B, Xiao X, Yan S, Shi D. FOXP1 expression and its clinicopathologic significance in nodal and extranodal diffuse large B-cell lymphoma. Ann Hematol. 2011;90(6):701–708. [PubMed]
  84. Sagardoy A, Martinez-Ferrandis JI, Roa S, et al. Downregulation of FOXP1 is required during germinal center B-cell function. Blood. 2013;121(21):4311–4320. [PMC free article] [PubMed]
  85. Hu CR, Wang JH, Wang R, Sun Q, Chen LB. Both FOXP1 and p65 expression are adverse risk factors in diffuse large B-cell lymphoma: a retrospective study in China. Acta Histochem. 2013;115(2):137–143.[PubMed]
  86. Ladanyi M, Offit K, Jhanwar SC, Filippa DA, Chaganti RS. MYC rearrangement and translocations involving band 8q24 in diffuse large cell lymphomas. Blood. 1991;77(5):1057–1063. [PubMed]
  87. Horn H, Ziepert M, Becher C, et al. MYC status in concert with BCL2 and BCL6 expression predicts outcome in diffuse large B-cell lymphoma. Blood. 2013;121(12):2253–2263. [PubMed]
  88. Whitten J, Arcila ME, Teruya-Feldstein J. Burkitt lymphoma. Pathol Case Rev. 2012;17:79–83.
  89. Miles RR, Arnold S, Cairo MS. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia. Br J Haematol. 2012;156(6):730–743. [PubMed]
  90. de Leval L, Hasserjian RP. Diffuse large B-cell lymphomas and Burkitt lymphoma. Hematol Oncol Clin North Am. 2009;23(4):791–827. [PubMed]
  91. Linch DC. Burkitt lymphoma in adults. Br J Haematol. 2012;156(6):693–703. [PubMed]
  92. De Roos AJ, Mirick DK, Edlefsen KL, et al. Markers of B-cell activation in relation to risk of non-Hodgkin lymphoma. Cancer Res. 2012;72(18):4733–4743. [PMC free article] [PubMed]
  93. Mellgren K, Hedegaard CJ, Schmiegelow K, Müller K. Plasma cytokine profiles at diagnosis in pediatric patients with non-Hodgkin lymphoma. J Pediatr Hematol Oncol. 2012;34(4):271–275. [PubMed]
  94. Vendrame E, Martínez-Maza O. Assessment of pre-diagnosis biomarkers of immune activation and inflammation: insights on the etiology of lymphoma. J Proteome Res. 2011;10(1):113–119.[PMC free article] [PubMed]
  95. Masood R, Zhang Y, Bond MW, et al. Interleukin-10 is an autocrine growth factor for acquired immunodeficiency syndrome-related B-cell lymphoma. Blood. 1995;85(12):3423–3430. [PubMed]
  96. Powles T, Matthews G, Bower M. AIDS related systemic non-Hodgkin’s lymphoma. Sex Transm Infect.2000;76(5):335–341. [PMC free article] [PubMed]
  97. Vendrame E, Hussain SK, Breen EC, et al. Serum levels of cytokines and biomarkers for inflammation and immune activation, and HIV-associated non-Hodgkin B-cell lymphoma risk. Cancer Epidemiol Biomarkers Prev. 2014;23(2):343–349. [PMC free article] [PubMed]
  98. Nakayama S, Yokote T, Hirata Y, et al. TNF-α expression in tumor cells as a novel prognostic marker for diffuse large B-cell lymphoma, not otherwise specified. Am J Surg Pathol. 2014;38(2):228–234.[PubMed]
  99. Breen EC, Hussain SK, Magpantay L, et al. B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma. Cancer Epidemiol Biomarkers Prev. 2011;20(7):1303–1314. [PMC free article] [PubMed]
  100. Landgren O, Goedert JJ, Rabkin CS, et al. Circulating serum free light chains as predictive markers of AIDS-related lymphoma. J Clin Oncol. 2010;28(5):773–779. [PMC free article] [PubMed]
  101. Suzuki K, Terui Y, Nishimura N, et al. Prognostic value of C-reactive protein, lactase dehydrogenase and anemia in recurrent or refractory aggressive lymphoma. Jpn J Clin Oncol. 2013;43(1):37–44. [PubMed]
  102. Ratner L, Lee J, Tang S, et al. Chemotherapy for human immunodeficiency virus-associated non-Hodgkin’s lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol.2001;19(8):2171–2178. [PubMed]
  103. Ansell SM, Armitage J. Non-Hodgkin lymphoma: diagnosis and treatment. Mayo Clin Proc.2005;80(8):1087–1097. [PubMed]
  104. Levine AM. AIDS-related lymphoma. Semin Oncol Nurs. 2006;22(2):80–89. [PubMed]
  105. Milanovic N, Matkovic S, Ristic D, Jelic S, Petrovic M. Significance of tumor burden, vascular endothelial growth factor, lactate dehydrogenase and beta-2 microglobulin serum levels in advanced diffuse large B cell lymphoma. J BUON. 2012;17(3):497–501. [PubMed]
  106. Bairey O, Bar-Natan M, Shpilberg O. Early death in patients diagnosed with non-Hodgkin’s lymphoma. Ann Hematol. 2013;92(3):345–350. [PubMed]
  107. Matthews GV, Bower M, Mandalia S, Powles T, Nelson MR, Gazzard BG. Changes in acquired immunodeficiency syndrome-related lymphoma since the introduction of highly active antiretroviral therapy.Blood. 2000;96(8):2730–2734. [PubMed]
  108. Tedeschi R, Bortolin MT, Bidoli E, et al. Assessment of immunovirological features in HIV related non-Hodgkin lymphoma patients and their impact on outcome. J Clin Virol. 2012;53(4):297–301. [PubMed]
  109. Guiguet M, Boué F, Cadranel J, et al. Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol. 2009;10(12):1152–1159. [PubMed]
  110. Engels EA, Pfeiffer RM, Landgren O, Moore RD. Immunologic and virologic predictors of AIDS-related non-Hodgkin lymphoma in the highly active antiretroviral therapy era. J Acquir Immune Defic Syndr.2010;54(1):78–84. [PMC free article] [PubMed]
  111. Zoufaly A, Stellbrink HJ, Heiden MA, et al. Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma. J Infect Dis. 2009;200(1):79–87. [PubMed]
  112. Izadi-Mood N, Sarmadi S, Eftekhar Z, Jahanteegh HA, Sanii S. Immunohistochemical expression of p16 and HPV L1 capsid proteins as predictive markers in cervical lesions. Arch Gynecol Obstet. 2013[PubMed]
  113. Selvi K, Badhe BA, Papa D, Nachiappa Ganesh R. Role of p16, CK17, p63, and human papillomavirus in diagnosis of cervical intraepithelial neoplasia and distinction from its mimics. Int J Surg Pathol. 2013 [PubMed]
  114. Frumovitz M. Invasive Cervical Cancer: Epidemiology, Risk Factors, Clinical Manifestations, and Diagnosis. UpToDate. 2013. [Accessed December 11, 2013]. Available athttp://www.uptodate.com/contents/invasive-cervical-cancer-epidemiology-risk-factors-clinical-manifestations-and-diagnosis?source=search_result&search=cervical+cancer&selectedTitle=1~150.
  115. Madhumati G, Kavita S, Anju M, Uma S, Raj M. Immunohistochemical expression of cell proliferating nuclear antigen (PCNA) and p53 protein in cervical cancer. J Obstet Gynaecol India. 2012;62(5):557–561.[PMC free article] [PubMed]
  116. Campbell LM, Pitta DR, De Assis AM, Derchain SF, Campos EA, Sarian LO. Retrieval of HPV oncogenes E6 and E7 mRNA from cervical specimens using a manual open technology protocol.Springerplus. 2013;2:473. [PMC free article] [PubMed]
  117. Ratnam S, Coutlee F, Fontaine D, et al. Aptima HPV E6/E7 mRNA test is as sensitive as Hybrid Capture 2 Assay but more specific at detecting cervical precancer and cancer. J Clin Microbiol.2011;49(2):557–564. [PMC free article] [PubMed]
  118. Roncaglia MT, Fregnani JH, Tacla M, et al. Characterization of p16 and E6 HPV-related proteins in uterine cervix high-grade lesions of patients treated by conization with large loop excision. Oncol Lett.2013;6(1):63–68. [PMC free article] [PubMed]
  119. Tagle DK, Sotelo DH, Illades-Aguiar B, et al. Expression of E6, p53 and p21 proteins and physical state of HPV16 in cervical cytologies with and without low grade lesions. Int J Clin Exp Med.2014;7(1):186–193. [PMC free article] [PubMed]
  120. Benevolo M, Vocaturo A, Caraceni D, et al. Sensitivity, specificity, and clinical value of human papillomavirus (HPV) E6/E7 mRNA assay as a triage test for cervical cytology and HPV DNA test. J Clin Microbiol. 2011;49(7):2643–2650. [PMC free article] [PubMed]
  121. Sari Aslani F, Safaei A, Pourjabali M, Momtahan M. Evaluation of Ki67, p16 and CK17 markers in differentiating cervical intraepithelial neoplasia and benign lesions. Iran J Med Sci. 2013;38(1):15–21.[PMC free article] [PubMed]
  122. Lindström A. Prognostic Factors for Squamous Cell Cervical Cancer: Tumor Markers, Hormones, Smoking, and S-Phase Fraction. Umeå; 2010. [Accessed June 1, 2014]. Available at http://www.diva-portal.org/smash/get/diva2:318860/FULLTEXT01.pdf.
  123. Carozzi F, Gillio-Tos A, Confortini M, et al. Risk of high-grade cervical intraepithelial neoplasia during follow-up in HPV-positive women according to baseline p16-INK4A results: a prospective analysis of a nested substudy of the NTCC randomised controlled trial. Lancet Oncol. 2013;14(2):168–176. [PubMed]
  124. Iaconis L, Hyjek E, Ellenson LH, Pirog EC. p16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection. Arch Pathol Lab Med. 2007;131(9):1343–1349. [PubMed]
  125. Portari EA, Russomano FB, de Camargo MJ, et al. Immunohistochemical expression of cyclin D1, p16Ink4a, p21WAF1, and Ki-67 correlates with the severity of cervical neoplasia. Int J Gynecol Pathol.2013;32(5):501–508. [PubMed]
  126. Regauer S, Reich O. CK17 and p16 expression patterns distinguish (atypical) immature squamous metaplasia from high-grade cervical intraepithelial neoplasia (CIN III) Histopathology. 2007;50(5):629–635.[PMC free article] [PubMed]
  127. Martens JE, Arends J, Van der Linden PJ, De Boer BA, Helmerhorst TJ. Cytokeratin 17 and p63 are markers of the HPV target cell, the cervical stem cell. Anticancer Res. 2004;2(2B):771–775. [PubMed]
  128. Ikeda K, Tate G, Suzuki T, Mitsuya T. Coordinate expression of cytokeratin 8 and cytokeratin 17 immunohistochemical staining in cervical intraepithelial neoplasia and cervical squamous cell carcinoma: an immunohistochemical analysis and review of the literature. Gynecol Oncol. 2008;108(3):598–602. [PubMed]
  129. Ishimi Y, Okayasu I, Kato C, et al. Enhanced expression of MCM proteins in cancer cells derived from uterine cervix. Eur J Biochem. 2003;270(6):1089–1101. [PubMed]
  130. Das M, Prasad SB, Yadav SS, et al. Over expression of minichromosome maintenance genes is clinically correlated to cervical carcinogenesis. PLoS One. 2013;8(7):e69607. [PMC free article] [PubMed]
  131. Bonds L, Baker P, Gup C, Shroyer KR. Immunohistochemical localization of cdc6 in squamous and glandular neoplasia of the uterine cervix. Arch Pathol Lab Med. 2002;126(10):1164–1168. [PubMed]
  132. Murphy N, Ring M, Heffron CC, et al. Quantitation of CDC6 and MCM5 mRNA in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of the cervix. Mod Pathol. 2005;18(6):844–849. [PubMed]
  133. Cheng Q, Lau WM, Chew SH, Ho TH, Tay SK, Hui KM. Identification of molecular markers for the early detection of human squamous cell carcinoma of the uterine cervix. Br J Cancer. 2002;86(2):274–281.[PMC free article] [PubMed]
  134. Romus I, Triningsih FE, Mangunsudirdjo S, Harijadi A. Clinicopathology significance of p53 and p63 expression in Indonesian cervical squamous cell carcinomas. Asian Pac J Cancer Prev. 2013;14(12):7737–7741. [PubMed]
  135. Branca M, Ciotti M, Giorgi C, et al. Up-regulation of proliferating cell nuclear antigen (PCNA) is closely associated with high-risk human papillomavirus (HPV) and progression of cervical intraepithelial neoplasia (CIN), but does not predict disease outcome in cervical cancer. Eur J Obstet Gynecol Reprod Biol.2007;130(2):223–231. [PubMed]
  136. Zhou Y, Xu Q, Ling B, Xiao W, Liu P. Reduced expression of ΔNp63α in cervical squamous cell carcinoma. Clin Invest Med. 2011;34(3):E184–E191. [PubMed]
  137. Goel MM, Mehrotra A. Immunohistochemical expression of MIB-1 and PCNA in precancerous and cancerous lesions of uterine cervix. Indian J Cancer. 2013;50(3):200–205. [PubMed]
  138. Speiser P, Wanner C, Tempfer C, et al. CD44 is an independent prognostic factor in early-stage cervical cancer. Int J Cancer. 1997;74(2):185–188. [PubMed]
  139. Shimabukuro K, Toyama-Sorimachi N, Ozaki Y, et al. The expression patterns of standard and variant CD44 molecules in normal uterine cervix and cervical cancer. Gynecol Oncol. 1997;64(1):26–34. [PubMed]
  140. Dokmanovic L. Biomarkers in childhood non-Hodgkin’s lymphomas. Biomark Med. 2013;7(5):791–801. [PubMed]
  141. Hanash SM, Pitteri SJ, Faca VM. Mining the plasma proteome for cancer biomarkers. Nature.2008;452(7187):571–579. [PubMed]
  142. Bhatt AN, Mathur R, Farooque A, Verma A, Dwarakanath BS. Cancer biomarkers—current perspectives. Indian J Med Res. 2010;132:129–149. [PubMed]
  143. Chatterjee SK, Zetter BR. Cancer biomarkers: knowing the present and predicting the future. Future Oncol. 2005;1(1):37–50.


Source: Biomarkers in Cancer.