Molecular abnormalities in ovarian carcinoma: Clinical, morphological and therapeutic correlates

Histopathology

Volumn 62, Issue 1, 2013, Pages 59-70

  Gurung, Ananta ^a   Hung, Tawny ^a   Morin, Jason ^a   Gilks, C Blake ^a  

^a UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

Clear cell carcinoma; Endometrioid carcinoma; Molecular pathology; Mucinous carcinoma; Ovarian carcinoma; Serous carcinoma

Indexed keywords

BETA CATENIN; BEVACIZUMAB; BRCA1 PROTEIN; BRCA2 PROTEIN; CARBOPLATIN; CISPLATIN; HEPATOCYTE NUCLEAR FACTOR 1BETA; IRINOTECAN; K RAS PROTEIN; MUCIN; PACLITAXEL; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 2A; PLATINUM DERIVATIVE; PROTEIN P53; SUNITINIB; TAXANE DERIVATIVE; TRASTUZUMAB;

ANEUPLOIDY; ANGIOGENESIS; CANCER MORTALITY; CELL CYCLE REGULATION; CELL DIFFERENTIATION; CHROMOSOMAL INSTABILITY; CLEAR CELL CARCINOMA; COLLOID CARCINOMA; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ENDOMETRIOID CARCINOMA; GENE AMPLIFICATION; GENE DELETION; GENE EXPRESSION; HIGH GRADE SEROUS CARCINOMA; HUMAN; IMMUNOHISTOCHEMISTRY; LOW GRADE SEROUS CARCINOMA; MISSENSE MUTATION; MITOSIS; MOLECULAR PATHOLOGY; NONSENSE MUTATION; OVARY CARCINOMA; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVIEW; SALPINGOOOPHORECTOMY; TREATMENT RESPONSE;

ADENOCARCINOMA; ADENOCARCINOMA, CLEAR CELL; ANTINEOPLASTIC AGENTS; CARCINOMA, ENDOMETRIOID; CYSTADENOCARCINOMA, MUCINOUS; CYSTADENOCARCINOMA, SEROUS; CYSTADENOMA, SEROUS; FEMALE; HUMANS; MUTATION; OVARIAN NEOPLASMS; TUMOR MARKERS, BIOLOGICAL;

EID: 84871126338     PISSN: 03090167     EISSN: 13652559     Source Type: Journal    
DOI: 10.1111/his.12033     Document Type: Review

References (103)

1. Tavassoli FA, Devilee P eds. World Health Organization classification of tumors: pathology and genetics. Tumours of the breast and female genital organs. Lyon: IARC Press, 2003; 113-196.
2. Singer G, Kurman RJ, Chang HW, Cho SK, Shih Ie M. Diverse tumorigenic pathways in ovarian serous carcinoma. Am. J. Pathol. 2002; 160; 1223-1228.
3. Shih Ie M, Kurman RJ. Ovarian tumorigenesis: a proposed model based on morphological and molecular genetic analysis. Am. J. Pathol. 2004; 164; 1511-1518.
4. Guth U, Huang DJ, Bauer G, Stieger M, Wight E, Singer G. Metastatic patterns at autopsy in patients with ovarian carcinoma. Cancer 2007; 110; 1272-1280.
5. Kobel M, Kalloger SE, Huntsman DG et al. Differences in tumor type in low-stage versus high-stage ovarian carcinomas. Int. J. Gynecol. Pathol. 2010; 29; 203-211.
6. Kobel M, Huntsman D, Gilks CB. Critical molecular abnormalities in high-grade serous carcinoma of the ovary. Expert Rev. Mol. Med. 2008; 10; e22.
7. Salvador S, Gilks B, Kobel M, Huntsman D, Rosen B, Miller D. The fallopian tube: primary site of most pelvic high-grade serous carcinomas. Int. J. Gynecol. Cancer 2009; 19; 58-64.
8. Heintz AP, Odicino F, Maisonneuve P et al. Carcinoma of the ovary. Int. J. Gynaecol. Obstet. 2003; 83(Suppl. 1); 135-166.
9. Al-Hussaini M, Stockman A, Foster H, McCluggage WG. Wt-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma. Histopathology 2004; 44; 109-115.
10. Han G, Gilks CB, Leung S et al. Mixed ovarian epithelial carcinomas with clear cell and serous components are variants of high-grade serous carcinoma: an interobserver correlative and immunohistochemical study of 32 cases. Am. J. Surg. Pathol. 2008; 32; 955-964.
11. Gilks CB, Ionescu DN, Kalloger SE et al. Tumor cell type can be reproducibly diagnosed and is of independent prognostic significance in patients with maximally debulked ovarian carcinoma. Hum. Pathol. 2008; 39; 1239-1251.
12. Roh MH, Yassin Y, Miron A et al. High-grade fimbrial-ovarian carcinomas are unified by altered p53, pten and pax2 expression. Mod. Pathol. 2010; 23; 1316-1324.
13. Soslow RA, Han G, Park KJ et al. Morphologic patterns associated with brca1 and brca2 genotype in ovarian carcinoma. Mod. Pathol. 2012; 25; 625-636.
14. Ahmed AA, Etemadmoghadam D, Temple J et al. Driver mutations in tp53 are ubiquitous in high grade serous carcinoma of the ovary. J. Pathol. 2010; 221; 49-56.
15. Tomasini R, Mak TW, Melino G. The impact of p53 and p73 on aneuploidy and cancer. Trends Cell Biol. 2008; 18; 244-252.
16. Yemelyanova A, Vang R, Kshirsagar M et al. Immunohistochemical staining patterns of p53 can serve as a surrogate marker for tp53 mutations in ovarian carcinoma: an immunohistochemical and nucleotide sequencing analysis. Mod. Pathol. 2011; 24; 1248-1253.
17. Kobel M, Reuss A, Bois A et al. The biological and clinical value of p53 expression in pelvic high-grade serous carcinomas. J. Pathol. 2010; 222; 191-198.
18. Press JZ, De Luca A, Boyd N et al. Ovarian carcinomas with genetic and epigenetic brca1 loss have distinct molecular abnormalities. BMC Cancer 2008; 8; 17.
19. Venkitaraman AR. Linking the cellular functions of brca genes to cancer pathogenesis and treatment. Annu. Rev. Pathol. 2009; 4; 461-487.
20. The Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474; 609-615.
21. Piek JM, van Diest PJ, Zweemer RP et al. Dysplastic changes in prophylactically removed fallopian tubes of women predisposed to developing ovarian cancer. J. Pathol. 2001; 195; 451-456.
22. Mehra K, Mehrad M, Ning G et al. Stics, scouts and p53 signatures; a new language for pelvic serous carcinogenesis. Front. Biosci. (Elite Edn) 2011; 3; 625-634.
23. Przybycin CG, Kurman RJ, Ronnett BM, Shih Ie M, Vang R. Are all pelvic (nonuterine) serous carcinomas of tubal origin? Am. J. Surg. Pathol. 2010; 34; 1407-1416.
24. Kindelberger DW, Lee Y, Miron A et al. Intraepithelial carcinoma of the fimbria and pelvic serous carcinoma: evidence for a causal relationship. Am. J. Surg. Pathol. 2007; 31; 161-169.
25. Lee Y, Miron A, Drapkin R et al. A candidate precursor to serous carcinoma that originates in the distal fallopian tube. J. Pathol. 2007; 211; 26-35.
26. Sehdev AS, Kurman RJ, Kuhn E, Shih Ie M. Serous tubal intraepithelial carcinoma upregulates markers associated with high-grade serous carcinomas including rsf-1 (hbxap), cyclin e and fatty acid synthase. Mod. Pathol. 2010; 23; 844-855.
27. Kurman RJ, Shih Ie M. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am. J. Surg. Pathol. 2010; 34; 433-443.
28. Callahan MJ, Crum CP, Medeiros F et al. Primary fallopian tube malignancies in brca-positive women undergoing surgery for ovarian cancer risk reduction. J. Clin. Oncol. 2007; 25; 3985-3990.
29. Gilks CB, Prat J. Ovarian carcinoma pathology and genetics: recent advances. Hum. Pathol. 2009; 40; 1213-1223.
30. Drew Y, Mulligan EA, Vong WT et al. Therapeutic potential of poly(adp-ribose) polymerase inhibitor ag014699 in human cancers with mutated or methylated brca1 or brca2. J. Natl Cancer Inst. 2011; 103; 334-346.
31. Audeh MW, Carmichael J, Penson RT et al. Oral poly(adp-ribose) polymerase inhibitor olaparib in patients with brca1 or brca2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010; 376; 245-251.
32. Tutt A, Robson M, Garber JE et al. Oral poly(adp-ribose) polymerase inhibitor olaparib in patients with brca1 or brca2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010; 376; 235-244.
33. Ledermann J, Harter P, Gourley C et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N. Engl. J. Med. 2012; 366; 1382-1392.
34. Gelmon KA, Tischkowitz M, Mackay H et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol. 2011; 12; 852-861.
35. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a gynecologic oncology group study. J. Clin. Oncol. 2007; 25; 5165-5171.
36. Cannistra SA, Matulonis UA, Penson RT et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J. Clin. Oncol. 2007; 25; 5180-5186.
37. Burger RA, Brady MF, Bookman MA et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl. J. Med. 2011; 365; 2473-2483.
38. Perren TJ, Swart AM, Pfisterer J et al. A phase 3 trial of bevacizumab in ovarian cancer. N. Engl. J. Med. 2011; 365; 2484-2496.
39. Mackay HJ, Brady MF, Oza AM et al. Prognostic relevance of uncommon ovarian histology in women with stage III/IV epithelial ovarian cancer. Int. J. Gynecol. Cancer 2010; 20; 945-952.
40. Piccart MJ, Bertelsen K, James K et al. Randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J. Natl Cancer Inst. 2000; 92; 699-708.
41. Vasey PA, Jayson GC, Gordon A et al. Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J. Natl Cancer Inst. 2004; 96; 1682-1691.
42. Itamochi H, Kigawa J, Terakawa N. Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. Cancer Sci. 2008; 99; 653-658.
43. Sugiyama T, Kamura T, Kigawa J et al. Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer 2000; 88; 2584-2589.
44. Ho CM, Huang YJ, Chen TC et al. Pure-type clear cell carcinoma of the ovary as a distinct histological type and improved survival in patients treated with paclitaxel-platinum-based chemotherapy in pure-type advanced disease. Gynecol. Oncol. 2004; 94; 197-203.
45. Pectasides D, Fountzilas G, Aravantinos G et al. Advanced stage clear-cell epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol. Oncol. 2006; 102; 285-291.
46. Utsunomiya H, Akahira J, Tanno S et al. Paclitaxel-platinum combination chemotherapy for advanced or recurrent ovarian clear cell adenocarcinoma: a multicenter trial. Int. J. Gynecol. Cancer 2006; 16; 52-56.
47. Enomoto T, Kuragaki C, Yamasaki M et al. Is clear cell carcinoma and mucinous carcinoma of the ovary sensitive to combination chemotherapy with paclitaxel and carboplatin? Proc. Am. Soc. Clin. Oncol. 2003; 22 Abstract: 1797.
48. DeLair D, Oliva E, Kobel M, Macias A, Gilks CB, Soslow RA. Morphologic spectrum of immunohistochemically characterized clear cell carcinoma of the ovary: a study of 155 cases. Am. J. Surg. Pathol. 2011; 35; 36-44.
49. Reisman D, Glaros S, Thompson EA. The SWI/SNF complex and cancer. Oncogene 2009; 28(1653-166); 8.
50. Wiegand KC, Shah SP, Al-Agha OM et al. Arid1a mutations in endometriosis-associated ovarian carcinomas. N. Engl. J. Med. 2010; 363; 1532-1543.
51. Jones S, Wang TL, Shih Ie M et al. Frequent mutations of chromatin remodeling gene arid1a in ovarian clear cell carcinoma. Science 2010; 330; 228-231.
52. Yamamoto S, Tsuda H, Takano M, Iwaya K, Tamai S, Matsubara O. Pik3ca mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma. J. Pathol. 2011; 225; 189-194.
53. Eichhorn PJ, Creyghton MP, Bernards R. Protein phosphatase 2a regulatory subunits and cancer. Biochim. Biophys. Acta 2009; 1795; 1-15.
54. Janssens V, Goris J, Van Hoof C. Pp2a: the expected tumor suppressor. Curr. Opin. Genet. Dev. 2005; 15; 34-41.
55. McConechy MK, Anglesio MS, Kalloger SE et al. Subtype-specific mutation of pp p2r1a in endometrial and ovarian carcinomas. J. Pathol. 2011; 223; 567-573.
56. Shih Ie M, Panuganti PK, Kuo KT et al. Somatic mutations of ppp2r1a in ovarian and uterine carcinomas. Am. J. Pathol. 2011; 178; 1442-1447.
57. Tsuchiya A, Sakamoto M, Yasuda J et al. Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-1 beta as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am. J. Pathol. 2003; 163; 2503-2512.
58. Kobel M, Kalloger SE, Carrick J et al. A limited panel of immunomarkers can reliably distinguish between clear cell and high-grade serous carcinoma of the ovary. Am. J. Surg. Pathol. 2009; 33; 14-21.
59. Stany MP, Vathipadiekal V, Ozbun L et al. Identification of novel therapeutic targets in microdissected clear cell ovarian cancers. PLoS ONE 2011; 6; e21121.
60. Anglesio MS, Carey MS, Kobel M, Mackay H, Huntsman DG. Clear cell carcinoma of the ovary: a report from the first ovarian clear cell symposium, June 24th, 2010. Gynecol. Oncol. 2011; 121; 407-415.
61. Lu F GC, Mulligan AM, Ryan P et al. Prevalence of loss of expression of DNA mismatch repair proteinsin primary epithelial ovarian tumors. Int. J. Gynecol. Pathol. 2012; 31; 524-531.
62. Wells M. Recent advances in endometriosis with emphasis on pathogenesis, molecular pathology, and neoplastic transformation. Int. J. Gynecol. Pathol. 2004; 23; 316-320.
63. Van Gorp T, Amant F, Neven P, Vergote I, Moerman P. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract. Res. Clin. Obstet. Gynaecol. 2004; 18; 349-371.
64. Anglesio MS, George J, Kulbe H et al. Il6-stat3-hif signaling and therapeutic response to the angiogenesis inhibitor sunitinib in ovarian clear cell cancer. Clin. Cancer Res. 2011; 17; 2538-2548.
65. Swenerton KD, Santos JL, Gilks CB et al. Histotype predicts the curative potential of radiotherapy: the example of ovarian cancers. Ann. Oncol. 2011; 22; 341-347.
66. Kuo KT, Mao TL, Jones S et al. Frequent activating mutations of pik3ca in ovarian clear cell carcinoma. Am. J. Pathol. 2009; 174; 1597-1601.
67. Stewart CJ, Brennan BA, Chan T, Netreba J. Wt1 expression in endometrioid ovarian carcinoma with and without associated endometriosis. Pathology 2008; 40; 592-599.
68. Kobel M, Kalloger SE, Santos JL, Huntsman DG, Gilks CB, Swenerton KD. Tumor type and substage predict survival in stage I and II ovarian carcinoma: insights and implications. Gynecol. Oncol. 2010; 116; 50-56.
69. Gilks CB. Subclassification of ovarian surface epithelial tumors based on correlation of histologic and molecular pathologic data. Int. J. Gynecol. Pathol. 2004; 23; 200-205.
70. Kurman RJ, Shih Ie M. Molecular pathogenesis and extraovarian origin of epithelial ovarian cancer - shifting the paradigm. Hum. Pathol. 2011; 42; 918-931.
71. Tabrizi AD, Kalloger SE, Kobel M et al. Primary ovarian mucinous carcinoma of intestinal type: significance of pattern of invasion and immunohistochemical expression profile in a series of 31 cases. Int. J. Gynecol. Pathol. 2010; 29; 99-107.
72. Anglesio M, Kommoss S, Tolcher M et al. Molecular characterization of mucinous ovarian tumors supports a stratified treatment approach with her2 targeting in 18% of carcinomas. J. Pathol. 2012; [Epub ahead of print].
73. Schiavone MB, Herzog TJ, Lewin SN et al. Natural history and outcome of mucinous carcinoma of the ovary. Am. J. Obstet. Gynecol. 2011; 205; 480e.1-8.
74. Ludwick C, Gilks CB, Miller D, Yaziji H, Clement PB. Aggressive behavior of stage I ovarian mucinous tumors lacking extensive infiltrative invasion: a report of four cases and review of the literature. Int. J. Gynecol. Pathol. 2005; 24; 205-217.
75. Cuatrecasas M, Villanueva A, Matias-Guiu X, Prat J. K-ras mutations in mucinous ovarian tumors: a clinicopathologic and molecular study of 95 cases. Cancer 1997; 79; 1581-1586.
76. Gemignani ML, Schlaerth AC, Bogomolniy F et al. Role of kras and braf gene mutations in mucinous ovarian carcinoma. Gynecol. Oncol. 2003; 90; 378-381.
77. Mayr D, Hirschmann A, Lohrs U, Diebold J. Kras and braf mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol. Oncol. 2006; 103; 883-887.
78. McAlpine JN, Wiegand KC, Vang R et al. Her2 overexpression and amplification is present in a subset of ovarian mucinous carcinomas and can be targeted with trastuzumab therapy. BMC Cancer 2009; 9; 433.
79. Mok SC, Bell DA, Knapp RC et al. Mutation of k-ras protooncogene in human ovarian epithelial tumors of borderline malignancy. Cancer Res. 1993; 53; 1489-1492.
80. Ichikawa Y, Nishida M, Suzuki H et al. Mutation of k-ras protooncogene is associated with histological subtypes in human mucinous ovarian tumors. Cancer Res. 1994; 54; 33-35.
81. Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am. J. Surg. Pathol. 2003; 27; 985-993.
82. Vang R, Gown AM, Zhao C et al. Ovarian mucinous tumors associated with mature cystic teratomas: morphologic and immunohistochemical analysis identifies a subset of potential teratomatous origin that shares features of lower gastrointestinal tract mucinous tumors more commonly encountered as secondary tumors in the ovary. Am. J. Surg. Pathol. 2007; 31; 854-869.
83. Hess V, A'Hern R, Nasiri N et al. Mucinous epithelial ovarian cancer: a separate entity requiring specific treatment. J. Clin. Oncol. 2004; 22; 1040-1044.
84. Pectasides D, Fountzilas G, Aravantinos G et al. Advanced stage mucinous epithelial ovarian cancer: the Hellenic Cooperative Oncology Group experience. Gynecol. Oncol. 2005; 97; 436-441.
85. Pignata S, Ferrandina G, Scarfone G et al. Activity of chemotherapy in mucinous ovarian cancer with a recurrence free interval of more than 6 months: results from the socrates retrospective study. BMC Cancer 2008; 8; 252.
86. Russo A, Rizzo S, Bronte G et al. The long and winding road to useful predictive factors for anti-egfr therapy in metastatic colorectal carcinoma: the kras/braf pathway. Oncology 2009; 77(Suppl 1); 57-68.
87. Laurent-Puig P, Cayre A, Manceau G et al. Analysis of pten, braf, and egfr status in determining benefit from cetuximab therapy in wild-type kras metastatic colon cancer. J. Clin. Oncol. 2009; 27; 5924-5930.
88. Gilks CB. Molecular abnormalities in ovarian cancer subtypes other than high-grade serous carcinoma. J. Oncol. 2010; 2010; doi:10.1155/2010/740968.
89. Ali RH KS, Santos JL, Swenerton KD, Gilks CB. Stage II-IV low-grade serous carcinoma of the ovary is associated with a poor prognosis: a clinicopathological study of 32 patients from a population-based tumor registry. Int. J. Gynecol. Pathol. 31; 499-506.
90. Malpica A, Deavers MT, Lu K et al. Grading ovarian serous carcinoma using a two-tier system. Am. J. Surg. Pathol. 2004; 28; 496-504.
91. Malpica A, Deavers MT, Tornos C et al. Interobserver and intraobserver variability of a two-tier system for grading ovarian serous carcinoma. Am. J. Surg. Pathol. 2007; 31; 1168-1174.
92. Jones S, Wang TL, Kurman RJ et al. Low-grade serous carcinomas of the ovary contain very few point mutations. J. Pathol. 2012; 226; 413-420.
93. Hsu CY, Bristow R, Cha MS et al. Characterization of active mitogen-activated protein kinase in ovarian serous carcinomas. Clin. Cancer Res. 2004; 10; 6432-6436.
94. Singer G, Oldt R III, Cohen Y et al. Mutations in braf and kras characterize the development of low-grade ovarian serous carcinoma. J. Natl Cancer Inst. 2003; 95; 484-486.
95. Wong KK, Tsang YT, Deavers MT et al. Braf mutation is rare in advanced-stage low-grade ovarian serous carcinomas. Am. J. Pathol. 2010; 177; 1611-1617.
96. Wang SE, Narasanna A, Perez-Torres M et al. Her2 kinase domain mutation results in constitutive phosphorylation and activation of her2 and egfr and resistance to egfr tyrosine kinase inhibitors. Cancer Cell 2006; 10; 25-38.
97. Ho CL, Kurman RJ, Dehari R, Wang TL, Shih Ie M.. Mutations of braf and kras precede the development of ovarian serous borderline tumors. Cancer Res. 2004; 64; 6915-6918.
98. May T, Virtanen C, Sharma M et al. Low malignant potential tumors with micropapillary features are molecularly similar to low-grade serous carcinoma of the ovary. Gynecol. Oncol. 2010; 117; 9-17.
99. Staebler A, Heselmeyer-Haddad K, Bell K et al. Micropapillary serous carcinoma of the ovary has distinct patterns of chromosomal imbalances by comparative genomic hybridization compared with atypical proliferative serous tumors and serous carcinomas. Hum. Pathol. 2002; 33; 47-59.
100. Dehari R, Kurman RJ, Logani SShih Ie M.. The development of high-grade serous carcinoma from atypical proliferative (borderline) serous tumors and low-grade micropapillary serous carcinoma: a morphologic and molecular genetic analysis. Am. J. Surg. Pathol. 2007; 31; 1007-1012.
101. Gershenson DM, Sun CC, Bodurka D et al. Recurrent low-grade serous ovarian carcinoma is relatively chemoresistant. Gynecol. Oncol. 2009; 114; 48-52.
102. Gershenson DM, Sun CC, Iyer RB et al. Hormonal therapy for recurrent low-grade serous carcinoma of the ovary or peritoneum. Gynecol. Oncol. 2012; 125; 661-666.
103. Kohno M, Tanimura S, Ozaki K. Targeting the extracellular signal-regulated kinase pathway in cancer therapy. Biol. Pharm. Bull. 2011; 34; 1781-1784.