early stage epithelial ovarian cancers: a study of morphologic prognostic factors

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ARTICLE IN PRESS Model

RP 51019 1–6

Pathology – Research and Practice xxx (2013) xxx– xxx

Contents lists available at SciVerse ScienceDirect

Pathology – Research and Practice

j ourna l ho mepage: www.elsev ier .com/ locate /prp

riginal article

arly stage epithelial ovarian cancers: A study of morphologic prognostic factors

ysen Terzia,∗, Isıl Yıldız Aktasb, Anıl Dolgunc, Ali Ayhand, Türkan Küc ükali e, Alp Usubütüne

Department of Pathology, Baskent University Medical School, Bahcelievler, 06490 Ankara, TurkeyDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USADepartment of Biostatistics, Hacettepe University Medical School, Sihhiye, 06100 Ankara, TurkeyDepartment of Oncologic Gynecology, Baskent University Medical School, Bahcelievler, 06490 Ankara, TurkeyDepartment of Pathology, Hacettepe University Medical School, Sihhiye, 06100 Ankara, Turkey

r t i c l e i n f o

rticle history:eceived 9 July 2012eceived in revised form 11 February 2013ccepted 6 March 2013

eywords:arly ovarian carcinomarognosisniversal grade

a b s t r a c t

We intended to reevaluate the morphologic prognostic factors for early-stage ovarian carcinomas. Wereviewed 111 patients diagnosed with early-stage ovarian cancer who had undergone primary surgeryat Hacettepe Hospital between 1984 and 2001, using diagnostic criteria from the WHO-2003 classifica-tion. We applied the Universal grading system suggested by Shimizu/Silverberg and noted FIGO-stage,histotype, tumor size, bilaterality, and endometriosis. These features were compared with each other andsurvival. The survival analysis was carried out by Kaplan–Meier curves. Of the cases, 52 were reclassifiedas ‘borderline tumor’ or ‘cystadenoma with borderline foci’ and 59 as ‘invasive carcinoma’. FIGO-stageand mitotic count were significant for survivals of 59 patients with cancer. Mitotic index was also sig-

itosisIGO-stage

nificant for the probability of metastasis. The patients with stage-II cancer had 5.65 times more risk ofrecurrence than stage-I cancer. The 5-year overall and disease-free survivals rates were 90.6% and 87.5%for stage-I, 54.7% and 39.3% for stage-II, respectively. Universal grade did not reach statistical significancefor survivals but it was related to FIGO-stage significantly. In conclusion, FIGO-stage is the most reliableprognosticator. Although prognostic value of universal grade is not significant, mitotic count may provideimportant prognostic information for early-stage ovarian carcinomas.

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ntroduction

Ovarian carcinoma is the second most frequent type of gyne-ological cancer. Approximately 70% of patients present with thisancer when it is an advanced stage. Although the survival of theatients with early-stage epithelial ovarian cancer is significantlyigher than those with advanced cancer, these patients have a 5-ear survival of 80% to 55% according to some authors [1]. Otheruthors have found higher 5-year survival: Disease Free SurvivalDFS) 79–91% and Cancer Specific Survival 85–93% [2].

The pathologic and clinical prognostic factors that have beenreviously described for early stage ovarian carcinomas are vari-ble and controversial. FIGO-stage, histologic grade, age, ruptureefore and during surgery, peritoneal cytology status, and ploid-

ty come into prominence as the independent prognostic factors in

Please cite this article in press as: A. Terzi, et al., Early stage epithelial ovarPract (2013), http://dx.doi.org/10.1016/j.prp.2013.03.009

any studies in English literature [2–8]. Some authors have iden-ified the histologic grade as the most convincing prognostic factoror DFS in early-stage ovarian carcinomas, and they have suggested

∗ Corresponding author at: Department of Pathology, Baskent University, Schoolf Medicine, Bahcelievler, 06490 Ankara, Turkey. Tel.: +90 3122126591;ax: +90 3122127572.

E-mail address: [email protected] (A. Terzi).

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344-0338/$ – see front matter © 2013 Published by Elsevier GmbH.ttp://dx.doi.org/10.1016/j.prp.2013.03.009

© 2013 Published by Elsevier GmbH.

that it should be used when deciding adjuvant therapy [5,6]. How-ever, there is no universally accepted system for grading this type of

cancer. The FIGO grading system (FGS) is one of the most commonly

used systems for ovarian carcinomas. It was originally designed to

grade uterine endometrial cancer according to the main architec-

tural structures of the tumors observed [9]. Colleagues from the

Shimizu/Silverberg group [10,11] introduced a grading system that

can be used for all histologic types of ovarian carcinomas, based

on architectural grade, nuclear pleomorphism, and mitotic activ-

ity. This system is called the Universal grading system (UGS), based

on the Nottingham system for grading of breast carcinoma. Some

authors [12,13] suggested that the UGS was superior to the FGS in

terms of the prediction of malignancies and the adaptability to all

histolologic type ovarian carcinomas.

The aim of the present study was to assess the prognostic signif-

icance of UGS and the effects of some clinicopathologic prognostic

factors in patients with early (FIGO-stage I/II) ovarian carcinoma.

Material and methods

ian cancers: A study of morphologic prognostic factors, Pathol. – Res.

One hundred and fifty-six women underwent primary surgery 58

with diagnosis of early-stage ovarian cancer at the Gyneco- 59

logical Oncology Department at Hacettepe University Hospital 60

between 1984 and 2001. This surgery consisted of a bilateral 61

dx.doi.org/10.1016/j.prp.2013.03.009

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ARTICLE IN PRESSG Model

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2 A. Terzi et al. / Pathology – Research and Practice xxx (2013) xxx– xxx

Table 1The initial diagnosis and final diagnosis of the 52 patients not included in the analyses.

Initial diagnosis Final diagnosis

Serous ca (n = 24) Serous borderline tm (n = 23) Serous cystad.wbf (n = 1)Mucinous ca (n = 22) Mucinous borderline tm (n = 17) Mucinous cystad.wbf (n = 4) Serous borderline tm (n = 1)Endometrioid ca (n = 2) Endometrioid borderline tm (n = 2)

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TD

Mixed ca (n = 4) Serous borderline tm (n = 2)

a, carcinoma; tm, tumor; cystad.wbf, cystadenoma with borderline foci.

alpingoopherectomy, total abdominal hysterectomy, bilateralelvic paraaortic lymph node dissection, and omentectomy,niformly. Some of the patients also had subsequently receivedhemotherapy and second-look laparotomy depending on tumortage and histotype. Clinical data were obtained from the patientslinical recording system of the hospital. We could not reachetailed information about chemotherapy. We excluded thoseases where slides were not available in our laboratory and wherebsolute data or microscopic features were not conclusive of pri-ary ovarian carcinoma. We reevaluated all hematoxylin and eosin

lides from paraffin-embedded tissues of 111 cases chosen fromhe 156 patients. The slides were reviewed blindly to the clinicalutcome, using current diagnostic criteria according to the Worldealth Organization 2003 classification, by a gynecologic patholo-ist. The following clinical and pathologic parameters were notedor cancer patients: FIGO-stage of disease, age, tumor size, associ-tion with endometriosis, presence of bilaterality, histopathologicrchitecture, nuclear pleomorphism, mitotic index, UGS, and FGSfor only the cases of endometrioid type carcinoma). These parame-ers were compared with each other and with survival. Additionallyt was noted if the patient had received adjuvant therapy or not.

All cases were graded by applying the criteria of the Silverbergroup assessing architectural pattern, nuclear atypia, and mitoticctivity, without regard to histologic subtype. The universal gradingas implemented in the section showing the most severe degree

f atypia chosen from each case and the tumors were graded asollows: Architectural score (predominant): Glandular = 1, Papil-ary = 2, and Solid = 3; Cytologycal score (Nuclear pleomorphism):light = 1, Moderate = 2, and Marked = 3; Mitotic index (number ofitotic figures per 10 high-power fields [1 HPF = 0.345 mm2] inost active area) was counted minimally in 3 sets of 10 HPFs and

he highest mitotic count per 10 HPFs was recorded; mitotic score:–9 = 1, 10–24 = 2, and 25 or >25 = 3; Grade 1 = total score (addinghree values obtained earlier) 3–5, Grade 2 = 6 or 7, and Grade 3 = 8r 9. Kaplan–Meier survival analyzes were performed for all threeriteria separately and for the whole universal grade [10,11].

Only endometrioid type carcinomas were also graded accordingo FGS, depending on the ratio of glandular or papillary structuresersus solid tumor growth. In this system, <5% solid growth isquivalent to Grade 1; 5–50% solid growth, Grade 2; and >50% solidumor growth, Grade 3. The grade of tumor (otherwise grade 1 or


rade 2) was raised by one grade when there was a marked nucleartypia unsuitably severe for architectural grade of the tumor [9].

The overall survival (OS) was measured from the date of primaryperation to the date of death; if the patient was still alive, the OS

able 2istribution of FIGO stage-substage and histologic type for 59 patients with early-stage o

Histologic type I (%) Ia Ib

Serous (n = 16) 8 (50) 3 2

Mucinous (n = 14) 12 (86) 10 1

Endometrioid (n = 16) 13 (81) 6 0

Mixed (n = 2) 2 (100) 1 0

Clear cell (n = 9) 7 (78) 2 0

Transitional cell (n = 1) 0 (0) 0 0

Undifferentiated (n = 1) 1 (100) 0 0

Total (n = 59) (%) 43 (73) 22 3

Serous cystad.wbf (n = 1) Endometrioid borderline tm (n = 1)

was measured to the date of last contact. The DFS was measuredfrom the date of diagnosis to the date of event with the exceptionof death; if the patient was still disease free, the DFS was measuredto the date of last contact.

Univariate survival analysis was performed by generatingKaplan–Meier curves, and the groups were compared using the

Log-Rank and Wilcoxon tests. Multivariable survival analysis wasassessed with the Cox proportional hazards regression model. Dif-

ferential expression of IGF2BP3 across the four histopathological

subtypes was assessed with contingency analysis, and statistical

differences were quantified using the Pearson’s chi-square test.

Sensitivity, specificity and the area under the ROC curve analyses

were used to assess the optimal cut-off value for the mitosis score.

For all analyses, a p-value <0.05 was considered statistically sig-

nificant. Statistical analyses were carried out using SPSS software

(version 15.0; SPSS, Chicago, IL, USA).

Results

Of the 111 patients reevaluated, 59 as invasive carcinoma, 46 asborderline epithelial tumor and 6 as cystadenoma with borderline

foci were found on rewiew. The initial diagnosis and final diagno-sis of the 52 patients not included in the analyses are presented in

Table 1. Reevaluations of histologic diagnosis of 59 patients with

invasive ovarian carcinoma were as follows; 16 (27.1%) serous car-

cinoma, 14 (23.7%) mucinous carcinoma, 16 (27.1%) endometrioid

carcinoma, 9 (15.3%) clear cell carcinoma, 2 (3.4%) mixed carci-

noma, 1 (1.7%) transitional cell carcinoma, 1 (1.7%) undifferentiated

carcinoma. Of these patients, 43 (72.9%) were stage I and 16 (27.1%)

stage II. The relationship of FIGO stage and histologic subtype for

the patients with early-stage ovarian carcinoma is shown in Table 2.

Half of the patients with serous carcinoma were stage II, but more

than 77% of patients with endometrioid or mucinous or clear cell

carcinoma were stage I. Interestingly, of 9 patients with clear cell

carcinoma, 5 (56%) pooled in substage Ic, 6 (67%) had adjuvant

chemotherapy, and 3 (33%) died from disease, Thirty-three (55.9%)

of all patients with carcinoma had adjuvant chemotherapy.

The mean age of our series of patient with early ovarian car-

cinoma was 51.3 years. The group of patients with endometriosis

associated carcinoma had a younger age (mean age: 43 years) than

those with endometriosis unassociated, significantly (p = 0.03).


Endometriosis associated carcinoma was present in 14 (23.7%) of 146

59 patients; 8 endometrioid, 4 clear cell, 1 serous and 1 mucinous 147

type carcinoma. The relation between presence of endometrio- 148

sis and histotype of carcinoma was found statistically significant 149

varian carcinoma.

Ic II (%) IIa IIb IIc

3 8 (50) 2 0 61 2 (14) 0 2 07 3 (19) 0 0 31 0 (0) 0 0 05 2 (22) 1 0 10 1 (100) 0 0 11 0 (0) 0 0 0

18 16 (27) 3 2 11

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Table 3The mitotic index values for the four main histotypes.

Histotypea Mitotic indexa

N Mean Median Minimum Maximum Std. Deviation

Serous 16 16.11 14 5 42 11.77Mucinous 14 18.57 10 2 78 19.86Endometrioid 16 16.18 11,5 1 50 14.81Clear cell 9 7.35 9 1 16 4.80

1 78 14.57

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Fig. 1. The ROC curve for the mitotic score. The best cut-off value of mitotic indexfor detecting the recurrence was 17.5 (AUC = 0.701, p = 0.034). The sensitivity andspecificity values were 0.67 and 0.82, respectively.

Total 55 15.49 10

a The relation of mitotic index and histotype was not significant statistically (P =

p = 0.008). Endometriosis was mostly related to endometrioid andlear cell type cancers.

The mean value of mitotic index was 15.49 (range 1–78) for theour main histologic groups (serous, mucinous, endometrioid andlear cell). Those with the smallest mean mitotic index was clearell carcinoma; 7.35 (range 1–16) among these groups (Table 3).

The tumor sizes were varied from 4 cm to 30 cm. The com-arisons of histologic subtypes for tumor sizes demonstrated thatucinous type carcinomas had larger tumor sizes than serous,

ndometrioid and clear cell types carcinomas (Post Hoc Tests; = 0.03). There was bilaterality in 11 patients with ovarian cancer,nd 7 (77.8%) of them had serous carcinoma. There were 7 eventsf metastasis and 4 of them were to the liver, 2 to the lung and 1 tohe inguinal lymph nodes.

In the survival studies on 55 patients with carcinoma (thereere 4 lost of follow-up), median follow-up was 49 months (range

–185) for OS, and 5-year OS was 79.5%, and 5-year DFS was 73.2%,or all patients. In the univariated statistical analysis, FIGO stage,

itotic index and mitotic score were significant for survival butther parameters (grade, histotype, architectural score, cytology-al score, age, tumor size, presence of bilaterality or endometriosis)ere not. There were significant differences between stage I and

tage II patients for OS and DFS (p = 0.007 and p < 0.001, respec-ively) (Table 4).

Mitotic index was also highly significant for both OS and DFSp = 0.005 and p = 0.003, respectively). The best cut-off value in

itotic index for detecting the recurrence was found as 17.5AUC = 0.701, p = 0.034) (Sensitivity: 0.67; Specificity: 0.82). Therea below ROC curve that shows the success of mitosis numbern predicting the state of recurrence is 0.701, p = 0.034. The risk ofecurrence for the group that has 18 mitosis and more per 10 HPFs is.5 times more than those with <18 mitosis per 10 HPFs (HR = 7.5,

< 0.001, 95% CI 2.2–25.3). The performance of the mitotic indexor detecting mortality was not statistically significant (AUC = 0.60,

= 0.277). The ROC curve was demonstrated in Fig. 1.Mitotic score according to UGS was statistically significant for

FS (p = 0.014) and almost significant for OS (p = 0.06). Multipleomparison revealed that the DFS rates of patients with mitoticcore 1 were statistically different to those with mitotic score 3p = 0.008) (Fig. 2).

Please cite this article in press as: A. Terzi, et al., Early stage epithelial ovarian cancers: A study of morphologic prognostic factors, Pathol. – Res.Pract (2013), http://dx.doi.org/10.1016/j.prp.2013.03.009

The relation between numbers of mitosis and probability ofetastasis was statistically significant (Mann–Whitney-U test,

= 0.049); tumors of the patients with metastasis had a higheritotic index. The impact of mitotic index on survival for each

able 4elationship of 5-year survivals of patients with early stage ovarian carcinoma andIGO stage.

FIGO stage 5-year OS % 5-year DFS %

Stage I 90.6 87.5Stage II 54.7 39.3pa 0.007 <0.001

S, overall survival; DFS, disease free survival.a Differences are significant, p < 0.005 according to Log Rank Chi-square test.

Fig. 2. The impact of mitotic score on DFS (p = 0.014). Multiple comparison revealedthat the DFS rates of patients with mitotic score 1 and 3 is statistically different(p = 0.008).

dx.doi.org/10.1016/j.prp.2013.03.009


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4 A. Terzi et al. / Pathology – Research and Practice xxx (2013) xxx– xxx

Fig. 3. The images from mitoses in the examples of the various histologic tumors: (A) Clear cell carcinoma (hematoxylin and eosin, ×200), (B) Mucinous carcinoma withh ith lowh itotic

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igh mitotic index (hematoxylin and eosin, ×200), (C) Endometrioid carcinoma wigh mitotic index (hematoxylin and eosin, ×200), (E) Serous carcinoma with low mhematoxylin and eosin, ×200).

istologic group could not be accounted because of the smallumber of patients in the groups for Kaplan–Meier and ROCnalyses. So, the cut-off value could not be obtained for eachistotype. The images from mitoses in the examples of the variousistologic tumors were illustrated Fig. 3.


In the multivariated analysis, FIGO stage was seen to be the onlyignificant independent prognostic factor for DFS but, none of FIGOtages, mitotic index or mitotic score were significant for OS. Those

able 5elationship of tumor histotype and UGS for 55 patients with early stage ovarian carcino

UGSa Serous Mucinous

Grade 1 3(18.7%) 10 (71.4%)

Grade 2 11 (68.8%) 4 (28.6%)

Grade 3 2 (12.5%)b 0 (0%)

Total 16 (100.0%) 14 (100.0%)

a The relation between universal grade and histotype was statistically significant (p = 0b Grade 3 cases were only included by endometrioid carcinomas and serous carcinoma

mitotic index (hematoxylin and eosin, ×200), (D) Endometrioid carcinoma withindex (hematoxylin and eosin, ×100), (F) Serous carcinoma with high mitotic index

with stage II cancer had 5.65 times more risk of recurrence thanpatients with stage I cancer (p = 0.006).

UGS was not statistically significant for OS (p = 0.316) and DFS

(p = 0.08). While grade 3 cases had 4.93 times more risk of recur-

rence than grade 1 cases (Hazard Ratio), this difference did not


reach statistical significance in this study. UGS was related to FIGO 207

stage significantly (p = 0.028); stage I carcinomas were mostly grade 208

1, stage II carcinomas were mostly grade 2 or grade 3. The effect of 209

mas.

Endometrioid Clear cell Total

9 (56.2%) 4 (44.4%) 26 (47.3%)3 (18.8%) 5 (55.6%) 23 (41.8%)4 (25%)b 0 (0%) 6 (10.9%)

16 (100.0%) 9 (100.0%) 55 (100.0%)

.011).s.

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GS on survival for patients with endometrioid type cancer couldot be evaluated because of the small number of cases available

or Kaplan–Meier test. There was inconsistency between FGS andGS in 4 (25%) of 16 endometrioid carcinomas. FIGO grading of

hese cases was changed according to UGS; all of them were down-raded, either from Grade 3 to Grade 2 (2 cases), or from Grade 2o Grade 1.

Histological type was not found to have a significant influencen OS or DFS. The endometrioid carcinoma group had the highest88.9%), expectation of five-year OS while the clear cell carcinomaroup had the lowest (57.1%). The relation between UGS and histo-ype was significant (p = 0.011); grade 3 cases were only included byndometrioid carcinomas (66.7%) and serous carcinomas (33.3%).ucinous carcinomas and clear cell carcinomas were universal

rade 1 or 2 (Table 3). 81.3% of serous carcinomas and almost half ofndometrioid carcinomas pooled in universal grade 2 and 3 groupsTable 5).

iscussion

FIGO stage is a prognostic factor, universally accepted in ovarianarcinoma. We also found the stage as an independent prognos-ic factor for early stage ovarian carcinomas in the present study.he Commission on Cancer of the American College of Surgeonsas reported a national survey of patients with ovarian cancer. Inhis large scale study, the overall 5-year survivals were 88.9%; and7.1% for stages I, and II, respectively [7]. The results of our studyere very near these results (90.6%; and 54.7% for Stages I, and II,

espectively).Histologic grade is a controversial prognostic factor as there is

o single system universally accepted for grading all ovarian can-ers. It therefore lacks uniform criteria. However, some clinicalecisions take grade into account; patients with grade 1 ovarianarcinomas in FIGO stage Ia and Ib are widely accepted as low-isk early-stage cancer and do not receive adjuvant chemotherapy3]. The proposed change 10 the current FIGO staging system invarian cancers made by The Gynecologic Cancer Intergroup washat grading should be reported in early stage disease becausehey believe that grading ovarian carcinomas can have impor-ant implications for therapeutic decisions, in particular in FIGOtage I [14]. Some large scale-studies have reported that gradingrovides prognostic information in early-stage ovarian carcino-as [2–6]. The most commonly used grading system in previous

tudies was FGS, a three-tier system based on tumor architec-ure mainly. However, this grading system has a limitation that

akes impossible to apply it to all histologic types of ovarian car-inomas [9]. The UGS is a three-tier system, it is suggested thatt can be applied to ovarian carcinomas irrespective of histologicype. Although, we could not grade all histology in all three cate-ories; mucinous and clear cell carcinomas were only in two grades.his system consists of three criteria; architecture, nuclear pleo-orphism, and mitotic count. We tested separately, in our series,

rchitectural score, cytological score, mitotic score and universalrade, and mitotic index possessing prognostic relevance. We couldot show the prognostic importance of UGS, but it was related toIGO-stage significantly. However, mitotic index was highly sig-ificant for survivals and probability of metastasis. Mitotic scoreccording to UGS was significant for DFS but architectural andytological scores were not significant for survivals. These resultsighlighted the importance of mitotic index in grading early ovar-

an carcinomas. Shimizu at all [10] suggested that mitotic index was


n independent prognostic variable, incorporated into the grad-ng system and independent from nuclear pleomorphism. Theyound that mitotic index functioned well both in stage I/II and III/IVerous and mucinous carcinomas and also worked well in stage

PRESSnd Practice xxx (2013) xxx– xxx 5

I/II endometrioid carcinoma, but did not work in clear cell car-

cinoma, because more than 80% of them had mitotic index less

than 10, similarly to the results of our study. Mayr and Diebold

[13] found high mitotic activity to be associated with poor progno-

sis, but architectural pattern was not correlated with postoperative

outcome in their study. Haapasolo [15] emphasized the prognostic

power and reproducibility of mitotic index. Furthermore, Malpi-

cas 2-tiered system [16] (low-grade vs high-grade) has received

increasing acceptance for ovarian serous carcinoma recently. This

system is based primarily on the assessment of nuclear atypia with

the mitotic rate used as a secondary feature. According to this sys-

tem, low-grade tumors tend to have a lower mitotic rate (up to 12

mitoses per 10 HPFs), but those with high-grade have more than 12

mitosis per 10 HPFs. Aune et al. [17] found that mitotic index has a

prognostic role for ovarian carcinoma (early and advanced stages),

and those with the least median mitotic index is clear cell type; 8.5(2–16) among all the histologic groups they studied, parallel to our

findings.Our study found that the best cut-off value in the mitotic index

is 17.5 for detecting the recurrence, and a greater mitosis countis associated with lesser DFS time, significantly, for all patients in

our series. The difference between mitotic scores 1 and 3 was also

important for DFS. 25 ≤mitotic index is mitotic score 3 according to

UGS and is associated with poor DFS. So we can say that if a tumor

has 18 mitosis/10 HPFs or more, the risk of recurrence is 7.5 times

greater for early-stage ovarian carcinoma, except for the clear cell

type. Additional studies will be required to validate the utility of

this cut-off value for survival and therapeutic decisions for early

ovarian carcinomas.

Several studies showed that histotype is an independent prog-

nostic factor of survival for ovarian carcinomas and clear cell

histology have poorer prognosis mostly [18,19]. On the other hand,

serous histology was found to be significantly related with the

lymphatic involvement in several studies [19–21]. However, many

large scale studies performed on patients with early-stage ovarian

carcinoma failed to show prognostic value for the parameter for

survival [4–6,13]. The histotype or cell type were not found to have

a significant influence on OS or DFS in this study. Clear cell car-

cinoma are generally accepted as aggressive neoplasm. However

some studies imply that aggresive behavior is stage dependent. A

previous study showed that advanced-stage clear cell carcinomas

of the ovary indicated extremely poorer prognosis than the serous

type ovarian carcinomas, but those with early-stage did not [18].

Most of our clear cell carcinoma patients had indolent prognosis

but most of them were in stage I and had adjuvant chemotherapy.

According to the model suggested by Kurman and Shih [22],

assessing the ovarian tumors in two basic prognostic groups, type

I tumors include endometrioid and clear cell carcinomas and they

tend to be indolent neoplasms that arise from well characterized

precursor lesions; especially endometriosis. In contrast, Type II

tumors are aggressive and for them, well defined precursor lesions

have not been described. Furthermore, current molecular genetic

findings together with the morphological data support the view

that endometriosis is the common precursor for both endometrioid

and clear cell type carcinoma [23]. In our study, endometrio-

sis was found mostly associated with endometrioid and clear

cell type carcinomas, and only associated with other histotypes

in two cases (1 serous and 1 mucinous). However, endometrio-

sis had no any impact on prognosis of early stage ovarian

carcinoma.

In summary, this study highlighted that FIGO-stage is the most

reliable independent prognostic factor, but universal grade has


no statistically significant prognostic value for early-stage ovar- 335

ian carcinomas. However, mitotic index and mitotic score provide 336

important prognostic information, and are seen to be indispensable 337

components of grading systems for early-stage ovarian carcinomas.

dx.doi.org/10.1016/j.prp.2013.03.009

ING Model

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ARTICLERP 51019 1–6

A. Terzi et al. / Pathology – Rese

onflict of interest statement

None declared.

cknowledgments

Liu-zhi has participated in the design of the study, Zhou-meng,hang-jianzheng have contributed to the collection of the data,ai-heling, Sun-tiansheng have participated in the writing of theanuscript, and assumes full responsibility for the content of theanuscript. This study was supported by grants from Postdoctoral

cience Foundation of China (20100481516).

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early stage epithelial ovarian cancers: a study of morphologic prognostic factors

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