Impact of histology on disparities in survival between non-Hispanic black and non-Hispanic white women with epithelial ovarian cancer in Commission on Cancer®-accredited facilities
C. XuChunqiao TianChristopher M. TarneyKathryn Osei-BonsuMichael RichardsonJohn K. ChanRodney P. RocconiNathaniel JonesCraig D. ShriverNicholas W. BatemanThomas P. ConradsC.A. HamiltonYovanni CasablancaG. Larry MaxwellKathleen M. Darcy
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Serous carcinoma
Histology
Clear cell carcinoma
White (mutation)
There are several morphologic types of ovarian carcinoma. It has been shown that p16 is overexpressed in high-grade serous carcinoma but there has been little detailed comparison of p16 expression in the common types of ovarian carcinoma. The aim of this study was to compare p16 expression in ovarian carcinomas of serous, endometrioid, clear cell, and mucinous type with a view to ascertaining whether high expression in a primary ovarian carcinoma is specific for a serous neoplasm. We included problematic cases, which are difficult to type, such as poorly differentiated and undifferentiated carcinomas and serous carcinomas with clear cells. In these problematic groups, we compared p16 expression with that of WT1, which is known to be relatively specific for a serous phenotype. Cases of ovarian high-grade serous carcinoma (n=38), endometrioid carcinoma (n=15), clear cell carcinoma (n=12), and mucinous carcinoma (n=10) were stained with p16. Cases were scored both with respect to distribution of immunoreactivity (0–5) and intensity (0–3). An immunohistochemical composite score was also calculated (0–15) by multiplying the distribution and intensity scores. Serous carcinomas typically exhibited high p16 expression; there was statistically significant higher p16 expression in serous carcinomas compared with the other morphologic types. There was high p16 and WT1 expression in most undifferentiated carcinomas and in serous carcinomas with clear cells, suggesting that these represent variants of serous carcinoma. We have demonstrated that p16 is highly expressed in high-grade serous and undifferentiated carcinomas compared with other morphologic types of ovarian carcinoma. This may be useful, in conjunction with WT1, in the classification of problematic neoplasms. p16 may be involved in the pathogenesis of high-grade ovarian serous carcinomas, possibly through inactivation of retinoblastoma protein.
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Clear cell carcinoma
Cystadenocarcinoma
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A review of the pathology and cytopathology of 295 endometrial adenocarcinomas treated surgically at King Edward Memorial Hospital for Women, with full 5-year follow-up, revealed 16 cases of pure serous carcinoma (USC), 10 cases of mixed serous and endometrioid carcinoma with a predominant serous component (mixed USC-EAC) and six cases of mixed serous and endometrioid carcinoma with a predominant endometrioid component (mixed EAC-USC). The mixed carcinomas may be characterized microscopically by classical serous features side by side with classical endometrioid features, or additionally by features intermediate between the two. Many of these features are reproduced in preoperative cervicovaginal smears. USC and mixed USC-EAC were found to be indistinguishable clinically and prognostically, with an identical corrected 5-year survival of 40%, although numbers are small. Mixed EAC-USC (which contained 10-25% serous differentiation in this series), however, were similar in many respects to a control population of 95 EAC of Grade 2 and 3. The corrected 5-year survival in these two groups was 67% and 79%, respectively, which is not statistically significant in this small series. This study suggests that the behavior of a mixed tumor containing 50% or more serous differentiation is similar to that of pure serous carcinoma, and that the behavior of a mixed tumor containing less than 25% serous differentiation is similar to that of the other component. Given the poor correlation between pathologic findings in curettage and subsequent hysterectomy specimens, however, identification of any significant serous element in curettage material may prove vital in optimizing surgical and adjuvant therapy.
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[Purpose] To investigate the relationship of preoperative serous CA125 with clinicopathological features and prognosis in patients with epithelial ovarian carcinoma.[Methods] The relationship of preoperative serous CA125 with histologic type,grade,FIGO stage,ascites and survival in 279 cases with epithelial ovarian carcinoma were analyzed retrospectively.[Results] The median CA125 value for all 279 patients was 339.2 U/ml(range 3.6～20 220.0U/ml).Preoperative serous CA125 in serous carcinoma was significantly higher than that in non-serous carcinoma(P0.05).For non-serous carcinoma with different histologic types,preoperative serous CA125 in mucinous /clear cell carcinoma was significantly lower than that in serous carcinoma(P0.01),and no significant difference was found between other types of non-serous carcinoma.Preoperative serous CA125 in early stage(stage Ⅰ) patient was significantly lower than that in advanced stage(stage Ⅱ～Ⅳ) patient(P=0.000).For non-mucinous/clear cell carcinoma patient,lower serous CA125 was usually associated with early disease and fairly good prognosis.As compared,higher serous CA125 was usually connected with advanced diseases,among which those with highest CA125 level displayed better survival than those with intermediate CA125 level.[Conclusion] Preoperative serous CA125 might reflect the tumor load for serous and other non-mucinous/clear cell carcinoma in epithelial ovarian carcinoma.
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Cystadenocarcinoma
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Introduction The dualistic theory of ovarian carcinogenesis proposes that epithelial “ovarian” cancer is not one entity with several histological subtypes but a collection of different diseases arising from cells of different origin, some of which may not originate in the ovarian surface epithelium. Methods All cases referred to the Pan-Birmingham Gynaecological Cancer Centre with an ovarian, tubal, or primary peritoneal cancer between April 2006 and April 2012 were identified from the West Midlands Cancer Registry. Tumors were classified into type I (low-grade endometrioid, clear cell, mucinous, and low-grade serous) and type II (high-grade serous, high-grade endometrioid, carcinosarcoma, and undifferentiated) cancers. Results Ovarian (83.5%), tubal (4.3%), or primary peritoneal carcinoma (12.2%) were diagnosed in a total of 583 woman. The ovarian tumors were type I in 134 cases (27.5%), type II in 325 cases (66.7%), and contained elements of both type I and type II tumors in 28 cases (5.7%). Most tubal and primary peritoneal cases, however, were type II tumors: 24 (96.0%) and 64 (90.1%), respectively. Only 16 (5.8%) of the ovarian high-grade serous carcinomas were stage I at diagnosis, whereas 240 (86.6%) were stage III+. Overall survival varied between the subtypes when matched for stage. Stage III low-grade serous and high-grade serous carcinomas had a significantly better survival compared to clear cell and mucinous cases, P = 0.0134. There was no significant difference in overall survival between the high-grade serous ovarian, tubal, or peritoneal carcinomas when matched for stage (stage III, P = 0.3758; stage IV, P = 0.4820). Conclusions Type II tumors are more common than type I and account for most tubal and peritoneal cancers. High-grade serous carcinomas, whether classified as ovarian/tubal/peritoneal, seem to behave as one disease entity with no significant difference in survival outcomes, therefore supporting the proposition of a separate classification of “tubo-ovarian serous carcinoma”.
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The five main subtypes of ovarian surface epithelial carcinoma (high-grade serous, low-grade serous, endometrioid, clear cell and mucinous) are different diseases, with differences in genetic and environmental risk factors, precursor lesions, molecular events during oncogenesis, patterns of spread and response to treatment. With recent advances in surgical pathology, it is possible to reproducibly diagnose these subtypes in routine surgical pathology practice. This review examines these subtypes of ovarian carcinoma, focusing on differential diagnosis, molecular features and current treatment strategies. The increasing understanding of the molecular abnormalities associated with each subtype is leading to exploration and introduction of more subtype-specific treatment of ovarian carcinoma.
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Clear cell carcinoma
Molecular Pathology
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There are conflicting data about chemoresistance and prognosis in ovarian clear cell carcinoma (CCC). This could be due to significant interobserver variation in the diagnosis of CCC and other ovarian surface epithelial tumors containing clear cells. Thirty-two cases previously diagnosed as CCC, high-grade ovarian serous carcinoma (SC), and mixed surface epithelial carcinoma (SEC) with clear cell and serous components were reviewed by 4 gynecologic pathologists blinded to the original diagnoses. Interobserver reproducibility was evaluated. Each case was also assessed using immunohistochemical markers Wilm tumor 1, estrogen receptor, and p53. The interobserver reproducibility was greatest for pure CCC (kappa of 0.82), and lowest for the mixed SEC (kappa of 0.32). Moderate agreement was seen in the pure SC category (kappa of 0.59). All pure SC and most mixed SEC presented as stage III or IV diseases. Most pure CCC presented as stage I or II diseases. Immunoreactivities of the mixed SECs were similar to those of pure SC, but significantly different from those of pure CCC for Wilm tumor 1 (P=0.0011 for both components), estrogen receptor (P=0.0003 for clear cell component, P=0.0001 for serous component), and p53 (P=0.0062 for both components). The serous and clear cell components of mixed SEC showed higher mitotic rates than pure CCC (P=0.004 and P=0.023, respectively), but the mitotic rate of pure SC was similar to the mixed SEC. We conclude that (1) pure CCC is reproducibly diagnosed. (2) The diagnosis of mixed ovarian SEC with clear cell component is not reproducible. (3) Mixed SEC with clear cell and serous components show similar stage, mitotic activities, and immunoreactivities to those of pure SC, and likely represent SC with clear cell changes.
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Background: The family of polypeptide N-acetylgalactosanimyltransferases (GalNAc-Ts) are important factors in glycosylation in carcinomas. The purpose of this study was to investigate the clinical significance of GalNAc-T6 and its correlation with the prognosis of epithelial ovarian carcinoma. Materials and Methods: A total of 150 patients with epithelial ovarian carcinoma were enrolled and the relationship between GalNAc-T6 expression by immunohistochemistry and long-term survival was evaluated. Results: The expression of GalNAc-T6 was positive in 57.6% (34/59) of those with serous carcinoma, 85.3% (29/34) in mucinous carcinoma, 15.6% (5/27) in clear cell carcinoma, and 44% (14/25) in endometrioid carcinoma. In a Kaplan–Meier analysis of patients with grade 1 or 2 serous carcinoma, the 10-year overall survival rates were 47.4% in the GalNAc-T6-positive and 9.1% in the GalNAc-T6-negative groups (p=0.047). Conclusion: GalNAc-T6 expression in epithelial ovarian carcinoma was different according to pathological type. In low-grade serous carcinoma, GalNAc-T6 expression may contribute to improved long-term survival.
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Low-grade serous ovarian carcinoma and its high-grade serous ovarian carcinoma counterpart differ in their precursor lesions, molecular profile, natural history, and response to therapies. As such, low-grade serous ovarian carcinoma needs to be studied separately from high-grade serous ovarian carcinoma, despite challenges stemming from its rarity. A deeper understanding of the pathogenesis of low-grade serous ovarian carcinoma and the most common molecular defects and pathways involved in the carcinogenesis of the ovarian epithelium from normal to serous borderline ovarian tumors to low-grade serous ovarian carcinoma will help develop better therapies. By adopting targeted approaches there may be an opportunity to integrate novel therapies without the need for robust numbers in clinical trials. This manuscript will discuss low-grade serous ovarian carcinoma and focus on the arising treatments being developed with an improved understanding of the pathogenesis of this disease.
Serous carcinoma
Cystadenocarcinoma
Targeted Therapy
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