Molecular Technologies in Gynecologic Oncology


  • Ciro Comparetto Division of Obstetrics and Gynecology, City Hospital, Prato, Italy
  • Franco Borruto Centre Hospitalier Princesse Grace, Principality of Monaco, Monaco



Gynecologic malignancies, diagnosis, treatment, prevention, molecular biology, genetics.


In recent years, the application of molecular biological techniques to the diagnosis and treatment of cancer has proved successful. In this kind of pathologies, molecular diagnosis is of fundamental importance as it allows identification at a pre-symptomatic stage, and then in the early phase, of the subjects in which cancer disease is developing. Molecular diagnosis of tumors by deoxy-ribonucleic acid (DNA) analysis is conducted on biological samples such as urine, feces, sputum, vaginal swab, and blood, searching and identifying in the various samples for the presence of cell carriers of an altered genetic information. The sensitivity of this kind of analysis is so high as to be very reliable even in the presence in the sample of a few tumor cells, level not reachable through the traditional “tumor markers”. The achievement of a facilitated early diagnosis of the tumor and, consequently, through the organization of specific therapeutic interventions, the prevention of the invasiveness of the pathology, allow to insert this kind of analysis among the most important investigations in the field of cancer prevention. Molecular oncology examinations have targeted the mutational study of the most involved genes in the onset of hereditary and/or family cancers such as breast, ovary, colon, melanoma, stomach, thyroid, etc. In addition, given the growing focus on the molecular mechanisms underlying the individual response to conventional chemotherapeutic drugs and molecular targeted agents responsible for drug resistance, pharmacogenetics exams have been added to those of molecular oncology. Some genes, when altered and/or mutated, can cause the development of tumors. In some types of cancer, the mutation may affect only somatic cells: in this case, the development will manifest itself only in the subject carrier of the mutation. Otherwise, if the mutation affects germ cells genes, it may occur the possibility to convey to children a susceptibility to the development of tumors. In fact, a significant proportion of cancers are hereditary. For example, it is estimated that about 7% of breast cancers, 10% of ovarian cancers, and about 5-10% of colorectal cancers, are caused by recurrent mutations at specific genes level. The early detection of cancer, with the ability to identify individuals at risk of developing the disease, is now the best way to reduce mortality from it. Determining whether a person has a mutation in a gene involved in neoplastic transformation that predisposes to the development of cancer (susceptibility or genetic predisposition) can significantly decrease its incidence and mortality. For example, as a result of in-depth studies of families at risk, it has been estimated that women who have inherited mutations in breast cancer genes (BRCA1 or BRCA2) are likely to develop breast cancer in 87% of cases, compared with 10% of non-bearers. This probability falls to 44-60% in the case of ovarian cancer, compared with 1% probability of not carriers. In this area, basic research has been developed with the aim of contributing to the study of the molecular mechanisms of oncogenesis, which generally has multistage character, with an initial immortalization and cell transformation and subsequent tumor progression. In this regard, studies at the molecular and functional level have been focused on models of different types of cancer, e.g. melanoma. In parallel, it has been studied the possible oncogenetic role of certain families of genes that have a functional role in embryogenesis, and in general in cell proliferation/differentiation, e.g. homeotic (HOX) genes. The gene expression profiles of purified cancer cells can be evaluated by microarray technique, comparing them with those of normal cells: comparative analysis, based on specific software, allows the identification of genes selectively modulated in the genetic program of tumor cells, in particular of genes specifically involved in the onset and progression of tumors. The modern goal of cancer therapy is to eliminate the disease by minimizing trauma and paying attention to the quality of life (QOL). With the passing of time, there has been a change of therapeutic paradigms and we have gone from the objective of maximum tolerable treatment to that of minimum effective treatment. This clinical imperative has its foundation in the quick transfer of biological knowledges to the care, integrating molecular informations with the development of new treatment methods. Especially for a delicate operation, even psychologically, such as that for breast cancer. In this setting, we have focused particularly on the technique of sentinel lymph node, demonstrating the possibility to avoid the treatment of the axilla in patients at low risk of recurrence. The term “molecular targeted therapy” is used to refer to agents that target specific pathways activated in the processes of growth, survival, invasion, and metastasis of cancer cells and in tumor neo-angiogenesis. The large and perhaps excessive optimism, caused by the gradual deepening of the knowledges of these mechanisms, has received a further boost by the arrival on the therapeutic scene of imatinib and other drugs belonging to the class of targeted biomolecular agents, including some monoclonal antibodies (McAb) such as trastuzumab, rituximab, cetuximab, and bevacizumab, and some small molecules, already entered clinical practice. But the question we must ask is whether that enthusiasm is justified and supported by scientifically strong and clinically proven data. The difficulties encountered in the research and development of new truly effective molecules and the disappointing results obtained in the early life of some of these agents and, not least, the high costs of treatments must lead to greater caution. The medical oncologist has the inescapable duty to possess sufficient culture to be able to properly use these new therapies in his diagnosis and treatment decision-making.


Taylor RR, Teneriello MG, Nash JD, Park RC, Birrer MJ. The molecular genetics of gyn malignancies. Oncology (Williston Park) 1994; 8: 63-70.

Whitcomb BP. Gynecologic malignancies. Surg Clin North Am 2008; 88: 301-17.

Cass I, Baldwin RL, Karlan BY. Molecular advances in gynecologic oncology. Curr Opin Oncol 1999; 11: 394-400.

Taylor N, Mutch DG. Gynecologic manifestations of hereditary nonpolyposis colorectal cancer. From inherited to sporadic disease. Oncology (Williston Park) 2006; 20: 85-94.

Lu KH, Broaddus RR. Gynecologic Cancers in Lynch Syndrome/HNPCC. Fam Cancer 2005; 4: 249-54.

Silverberg SG. Molecular diagnosis and prognosis in gynecologic oncology. Arch Pathol Lab Med 1999; 123: 1035-40.

Maxwell GL, Carlson JW. Oncogenes in gynecologic oncology. Obstet Gynecol Surv 1996; 51: 710-7.

Berchuck A, Kohler MF, Marks JR, Wiseman R, Boyd J, Bast RC Jr. The p53 tumor suppressor gene frequently is altered in gynecologic cancers. Am J Obstet Gynecol 1994; 170: 246-52.

Scambia G, Lovergine S, Masciullo V. RB family members as predictive and prognostic factors in human cancer. Oncogene 2006; 25: 5302-8.

Benedet JL. Progress in gynecologic cancer detection and treatment. Int J Gynaecol Obstet 2000; 70: 135-47.

Runowicz CD, Fields AL. Screening for gynecologic malignancies: A continuing responsibility. Surg Oncol Clin N Am 1999; 8: 703-23.

Farghaly SA. Tumor markers in gynecologic cancer. Gynecol Obstet Invest 1992; 34: 65-72.

Geisler JP, Geisler HE. Tumor markers and molecular biological markers in gynecologic malignancies. Curr Opin Obstet Gynecol 2001; 13: 31-9.

Murphy SK, Bassil CF, Huang Z. Main principles and outcomes of DNA methylation analysis. Methods Mol Biol 2013; 1049: 67-74.

Huang Z, Bassil CF, Murphy SK. Bisulfite sequencing of cloned alleles. Methods Mol Biol 2013; 1049: 83-94.

Denny L. International perspective on the global advances in gynecologic oncology. Am Soc Clin Oncol Educ Book 2012: 330-4.

Horowitz N, Matulonis UA. New biologic agents for the treatment of gynecologic cancers. Hematol Oncol Clin North Am 2012; 26: 133-56.

Carroll AR, Coleman RL, Sood AK. Therapeutic advances in women’s cancers. Front Biosci (Schol Ed) 2011; 3: 82-97.

Chon HS, Hu W, Kavanagh JJ. Targeted therapies in gynecologic cancers. Curr Cancer Drug Targets 2006; 6: 333-63.

Previs RA, Coleman RL, Harris AL, Sood AK. Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin Cancer Res 2015; 21: 955-61.

Ortega E, Marti RM, Yeramian A, et al. Targeted therapies in gynecologic cancers and melanoma. Semin Diagn Pathol 2008; 25: 262-73.

Romero IL, Mukherjee A, Kenny HA, Litchfield LM, Lengyel E. Molecular pathways: trafficking of metabolic resources in the tumor microenvironment. Clin Cancer Res 2015; 21: 680-6.

Brouwer-Visser J, Huang GS. IGF2 signaling and regulation in cancer. Cytokine Growth Factor Rev 2015; 26: 371-7.

Leath CA 3rd, Douglas JT, Curiel DT, Alvarez RD. Single-chain antibodies: A therapeutic modality for cancer gene therapy (review). Int J Oncol 2004; 24: 765-71.

Scott CL, Mackay HJ, Haluska P Jr. Patient-derived xenograft models in gynecologic malignancies. Am Soc Clin Oncol Educ Book 2014: e258-66.

Kamat AA, Sood AK. The merits of vascular targeting for gynecologic malignancies. Curr Oncol Rep 2005; 7: 444-50.

Bottsford-Miller JN, Coleman RL, Sood AK. Resistance and escape from antiangiogenesis therapy: clinical implications and future strategies. J Clin Oncol 2012; 30: 4026-34.

Petrillo M, Scambia G, Ferrandina G. Novel targets for VEGF-independent anti-angiogenic drugs. Expert Opin Investig Drugs 2012; 21: 451-72.

Vaidya AP, Parnes AD, Seiden MV. Rationale and clinical experience with epidermal growth factor receptor inhibitors in gynecologic malignancies. Curr Treat Options Oncol 2005; 6: 103-14.

Thanapprapasr D, Hu W, Sood AK, Coleman RL. Moving beyond VEGF for anti-angiogenesis strategies in gynecologic cancer. Curr Pharm Des 2012; 18: 2713-9.

Zand B, Coleman RL, Sood AK. Targeting angiogenesis in gynecologic cancers. Hematol Oncol Clin North Am 2012; 26: 543-63.

Schmid BC, Oehler MK. Improvements in progression-free and overall survival due to the use of anti-angiogenic agents in gynecologic cancers. Curr Treat Options Oncol 2015; 16: 318.

Cuello MA, Nau M, Lipkowitz S. Apoptosis and the treatment of breast cancer. Breast Dis 2002; 15: 71-82.

Karki R, Seagle BL, Nieves-Neira W, Shahabi S. Taxanes in combination with biologic agents for ovarian and breast cancers. Anticancer Drugs 2014; 25: 536-54.

Radpour R, Barekati Z, Kohler C, Holzgreve W, Zhong XY. New trends in molecular biomarker discovery for breast cancer. Genet Test Mol Biomarkers 2009; 13: 565-71.

Morris M, Tortolero-Luna G, Malpica A, et al. Cervical intraepithelial neoplasia and cervical cancer. Obstet Gynecol Clin North Am 1996; 23: 347-410.

Tjalma WA, Van Waes TR, Van den Eeden LE, Bogers JJ. Role of human papillomavirus in the carcinogenesis of squamous cell carcinoma and adenocarcinoma of the cervix. Best Pract Res Clin Obstet Gynaecol 2005; 19: 469-83.

Mitchell MF, Hittelman WK, Lotan R, et al. Chemoprevention trials and surrogate end point biomarkers in the cervix. Cancer 1995; 76: 1956-77.<1956::AID-CNCR2820761312>3.0.CO;2-V

Schoell WM, Janicek MF, Mirhashemi R. Epidemiology and biology of cervical cancer. Semin Surg Oncol 1999; 16: 203-11.<203::AID-SSU2>3.0.CO;2-C

Wolf JK, Ramirez PT. The molecular biology of cervical cancer. Cancer Invest 2001; 19: 621-9.

Bae JH, Park JS. Emerging biomarkers in the detection, diagnosis and management of cervical dysplasia and carcinoma. Expert Opin Med Diagn 2007; 1: 305-14.

Clarke B, Chetty R. Cell cycle aberrations in the pathogenesis of squamous cell carcinoma of the uterine cervix. Gynecol Oncol 2001; 82: 238-46.

Wolf JK, Franco EL, Arbeit JM, et al. Innovations in understanding the biology of cervical cancer. Cancer 2003; 98: 2064-9.

Steller MA, Schiller JT. Human papillomavirus immunology and vaccine prospects. J Natl Cancer Inst Monogr 1996; 21: 145-8.

Murakami M, Gurski KJ, Steller MA. Human papillomavirus vaccines for cervical cancer. J Immunother 1999; 22: 212-8.

Nijhuis ER, Reesink-Peters N, Wisman GB, et al. An overview of innovative techniques to improve cervical cancer screening. Cell Oncol 2006; 28: 233-46.

Namkoong SE. Clinical application of HPV typing in cervical cancer. Int J Gynaecol Obstet 1995; 49 Suppl: S59-67.

Goodman A. HPV testing as a screen for cervical cancer. BMJ 2015; 350: h2372.

Willmott LJ, Sumner DA, Monk BJ. Biologics in cervical cancer therapy. J Natl Compr Canc Netw 2010; 8: 1417-23.

Legge F, Fuoco G, Lorusso D, et al. Pharmacotherapy of cer-vical cancer. Expert Opin Pharmacother 2010; 11: 2059-75.

Im SS, Monk BJ. New developments in the treatment of invasive cervical cancer. Obstet Gynecol Clin North Am 2002; 29: 659-72.

del Campo JM, Prat A, Gil-Moreno A, Pérez J, Parera M. Update on novel therapeutic agents for cervical cancer. Gynecol Oncol 2008; 110: S72-6.

Zagouri F, Sergentanis TN, Chrysikos D, Filipits M, Bartsch R. Molecularly targeted therapies in cervical cancer. A systematic review. Gynecol Oncol 2012; 126: 291-303.

Vici P, Mariani L, Pizzuti L, et al. Emerging biological treatments for uterine cervical carcinoma. J Cancer 2014; 5: 86-97.

Eskander RN, Tewari KS. Beyond angiogenesis blockade: targeted therapy for advanced cervical cancer. J Gynecol Oncol 2014; 25: 249-59.

Tewari KS, Monk BJ. New strategies in advanced cervical cancer: from angiogenesis blockade to immunotherapy. Clin Cancer Res 2014; 20: 5349-58.

Tomao F, Di Tucci C, Imperiale L, et al. Cervical cancer: are there potential new targets? An update on preclinical and clinical results. Curr Drug Targets 2014; 15: 1107-20.

Burke TW, Fowler WC Jr, Morrow CP. Clinical aspects of risk in women with endometrial carcinoma. J Cell Biochem Suppl 1995; 23: 131-6.

Yap OW, Matthews RP. Racial and ethnic disparities in cancers of the uterine corpus. J Natl Med Assoc 2006; 98: 1930-3.

Burke TW, Tortolero-Luna G, Malpica A, et al. Endometrial hyperplasia and endometrial cancer. Obstet Gynecol Clin North Am 1996; 23: 411-56.

Schmandt RE, Iglesias DA, Co NN, Lu KH. Understanding obesity and endometrial cancer risk: opportunities for prevention. Am J Obstet Gynecol 2011; 205: 518-25.

Boruban MC, Altundag K, Kilic GS, Blankstein J. From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures. Eur J Cancer Prev 2008; 17: 133-8.

Binder PS, Mutch DG. Update on prognostic markers for endometrial cancer. Womens Health (Lond Engl) 2014; 10: 277-88.

Berchuck A, Boyd J. Molecular basis of endometrial cancer. Cancer 1995; 76: 2034-40.<2034::AID-CNCR2820761321>3.0.CO;2-U

Zhou XC, Dowdy SC, Podratz KC, Jiang SW. Epigenetic considerations for endometrial cancer prevention, diagnosis and treatment. Gynecol Oncol 2007; 107: 143-53.

Bruchim I, Sarfstein R, Werner H. The IGF Hormonal Network in Endometrial Cancer: Functions, Regulation, and Targeting Approaches. Front Endocrinol (Lausanne) 2014; 5: 76.

Bansal N, Yendluri V, Wenham RM. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control 2009; 16: 8-13.

Iglesias DA, Bodurka DC. Personalized care in uterine cancer. Clin Adv Hematol Oncol 2012; 10: 797-805.

Thanapprapasr D, Cheewakriangkrai C, Likittanasombut P, Thanapprapasr K, Mutch DG. Targeted endometrial cancer therapy as a future prospect. Womens Health (Lond Engl) 2013; 9: 189-99.

Thanapprapasr D, Thanapprapasr K. Molecular therapy as a future strategy in endometrial cancer. Asian Pac J Cancer Prev 2013; 14: 3419-23.

Lu KH. Management of early-stage endometrial cancer. Semin Oncol 2009; 36: 137-44.

Altundag O, Dursun P, Ayhan A. Emerging drugs in endometrial cancers. Expert Opin Emerg Drugs 2010; 15: 557-68.

Elit L, Hirte H. Current status and future innovations of hormonal agents, chemotherapy and investigational agents in endometrial cancer. Curr Opin Obstet Gynecol 2002; 14: 67-73.

Gehrig PA, Bae-Jump VL. Promising novel therapies for the treatment of endometrial cancer. Gynecol Oncol 2010; 116: 187-94.

Lai CH, Huang HJ. The role of hormones for the treatment of endometrial hyperplasia and endometrial cancer. Curr Opin Obstet Gynecol 2006; 18: 29-34.

Vandenput I. Clinicopathologic study in uterine cancer. Facts Views Vis Obgyn 2011; 3: 189-202.

Westin SN, Broaddus RR. Personalized therapy in endometrial cancer: challenges and opportunities. Cancer Biol Ther 2012; 13: 1-13.

Thangaraju S, Subramani E, Chakravarty B, Chaudhury K. Therapeutic targeting of the TNF superfamily: a promising treatment for advanced endometrial adenocarcinoma. Gynecol Oncol 2012; 127: 426-32.

Amadio G, Masciullo V, Ferrandina MG, Scambia G. Emerging drugs for endometrial cancer. Expert Opin Emerg Drugs 2014; 19: 497-509.

Diver EJ, Foster R, Rueda BR, Growdon WB. The Therapeutic Challenge of Targeting HER2 in Endometrial Cancer. Oncologist 2015; pii: theoncologist.2015-0149

Sudo T. Molecular-targeted therapies for ovarian cancer: prospects for the future. Int J Clin Oncol 2012; 17: 424-9.

Tammela J, Odunsi K. Gene expression and prognostic significance in ovarian cancer. Minerva Ginecol 2004; 56: 495-502.

Legge F, Ferrandina G, Scambia G. From bio-molecular and technology innovations to clinical practice: focus on ovarian cancer. Ann Oncol 2006; 17 Suppl 7: vii46-8.

Mok SC, Kwong J, Welch WR, et al. Etiology and pathogenesis of epithelial ovarian cancer. Dis Markers 2007; 23: 367-76.

Kurman RJ, Shih IeM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 2010; 34: 433-43.

McCluskey LL, Dubeau L. Biology of ovarian cancer. Curr Opin Oncol 1997; 9: 465-70.

Daly MB, Dresher CW, Yates MS, et al. Salpingectomy as a means to reduce ovarian cancer risk. Cancer Prev Res (Phila) 2015; 8: 342-8.

Sørensen RD, Schnack TH, Karlsen MA, Høgdall CK. Serous ovarian, fallopian tube and primary peritoneal cancers: a common disease or separate entities – A systematic review. Gynecol Oncol 2015; 136: 571-81.

Rodriguez M, Dubeau L. Ovarian tumor development: insights from ovarian embryogenesis. Eur J Gynaecol Oncol 2001; 22: 175-83.

Landen CN Jr, Birrer MJ, Sood AK. Early events in the pathogenesis of epithelial ovarian cancer. J Clin Oncol 2008; 26: 995-1005.

Holschneider CH, Berek JS. Ovarian cancer: epidemiology, biology, and prognostic factors. Semin Surg Oncol 2000; 19: 3-10.<3::AID-SSU2>3.0.CO;2-S

Khalil I, Brewer MA, Neyarapally T, Runowicz CD. The potential of biologic network models in understanding the etiopathogenesis of ovarian cancer. Gynecol Oncol 2010; 116: 282-5.

Despierre E, Lambrechts D, Neven P, Amant F, Lambrechts S, Vergote I. The molecular genetic basis of ovarian cancer and its roadmap towards a better treatment. Gynecol Oncol 2010; 117: 358-65.

Munksgaard PS, Blaakaer J. The association between endometriosis and ovarian cancer: a review of histological, genetic and molecular alterations. Gynecol Oncol 2012; 124: 164-9.

Freedman RS, Deavers M, Liu J, Wang E. Peritoneal inflammation – A microenvironment for Epithelial Ovarian Cancer (EOC). J Transl Med 2004; 2: 23.

Thompson MS, Mok SC. Immunopathogenesis of ovarian cancer. Minerva Med 2009; 100: 357-70.

Chatterjee M, Tainsky MA. Autoantibodies as biomarkers for ovarian cancer. Cancer Biomark 2010-2011; 8: 187-201.

Nam EJ, Kim YT. Alteration of cell-cycle regulation in epithelial ovarian cancer. Int J Gynecol Cancer 2008; 18: 1169-82.

Berchuck A, Carney M. Human ovarian cancer of the surface epithelium. Biochem Pharmacol 1997; 54: 541-4.

Cunat S, Hoffmann P, Pujol P. Estrogens and epithelial ovarian cancer. Gynecol Oncol 2004; 94: 25-32.




How to Cite

Comparetto, C. ., & Franco Borruto. (2015). Molecular Technologies in Gynecologic Oncology. Journal of Cancer Research Updates, 4(4),  195–226.