Placental expression of miR-517-5p and miR-518f-5p: Fetal sex-specific relations with human fetoplacental growth.

OBJECTIVE: We aimed to assess association of chromosome 19 miRNA cluster microRNAs (miR-517-5p and miR-518f-5p) expression with maternal, placental and newborn parameters and with their potential angiogenesis-associated target genes ENG, VEGF and FLT in a set of 68 small- (SGA, n = 30) and appropriate- (AGA, n = 38) for gestational age full-term singleton pregnancies, in relation to fetal sex. STUDY DESIGN: In this retrospective case-control study, placental transcript abundances of miR-517-5p and miR-518f-5p were assessed by real-time quantitative PCR after normalization to reference miRNA, mir-16-5p. Placental transcript abundances of VEGF, FLT and ENG were assessed after normalizing to a set of reference genes. RESULTS: Placental miR-517-5p transcript abundance was negatively associated with birth weight [ß = -88.778, P = 0.006, 95% confidence interval (CI): -151.645, -25.911] and placental weight (ß = -14.683, P = 0.007, 95% CI: -25.254, -4.112) and this association with birth weight was specific to the AGA births (ß = -59.207, P = 0.037, 95% CI: -114.522, -3.891). miR-518f-5p transcript abundance was negatively associated with placental weight (ß = -6.250, P = 0.034, 95% CI: -11.940, -0.559) specifically in the AGA male births (n = 16). Placental VEGF transcript abundance was negatively associated with that of miR-517-5p specifically in SGA female births (n = 14; Spearman's ρ = -0.705, P = 0.005) and with miR-518f-5p transcript abundance specifically in SGA births (Spearman's ρ = -0.437, P = 0.016) and in SGA male births (n = 16; Spearman's ρ = -0.516, P = 0.041). CONCLUSION: We conclude that placental miR-517-5p could be playing a key role in the pathophysiology of fetal growth restriction, which can be potentially targeted through maternal lifestyle modifications for improving fetoplacental growth.

Fetal vascular malperfusion (FVM): diagnostic implications and clinical associations.

INTRODUCTION: Fetal vascular malperfusion (FVM) is diagnosed by the presence of vascular lesions in the muscularized fetal vessels in the placenta and the resultant changes in the downstream villi. The Amsterdam Placental Working Group recognizes two patterns of FVM namely segmental and global. The aim of this study was to estimate the frequency of FVM lesion in our population and to understand its neonatal associations. METHODS: Fifty-four placentas with FVM and 56 controls collected over 34 months. The maternal and neonatal details were collected from the case charts. The patterns and grades of FVM lesions were related to the clinical factors and significance analyzed statistically using the Chi-square test and t-test and p < .05 was considered significant. RESULTS: The frequency of FVM was 8.7%. The FVM group showed lower mean gestational age, birth weight, and placental weight with a higher frequency of IUGR. Poor neonatal survival, non-reassuring fetal status, neurological abnormalities, neonatal sepsis, asphyxia, low Apgar, and respiratory support requirement were significantly higher in the FVM group. A similar frequency of segmental and global lesions was seen. High grade lesions (n = 35) were common than low grade (n = 19). Neonatal associations were more often seen in segmental and high-grade lesions. DISCUSSION: In the absence of antenatal diagnostic tools to identify FVM, placental examination is critical and the only definitive method to diagnose FVM, which alerts the clinician to monitor for several neonatal morbidities. Identification and typing the lesion as per the new guidelines proves significant risk associations with specific types of FVM.

Villitis of unknown etiology (VUE): effect on placental size and association with clinical parameters.

OBJECTIVES: Villitis of unknown etiology (VUE) is an inflammatory placental lesion with immune-mediated pathogenesis, diagnosed by histopathological examination. It is one of the three placental lesions which tend to recur in subsequent pregnancies, the other two being chronic histiocytic intervillositis and massive fibrin deposition. The frequency of VUE and its association with maternal, obstetric and neonatal complications are variability reported in the literature. The aim of this study is to determine the frequency of VUE in the population studied and to observe the association of specific subtypes of villitis with clinical features, placental morphometric and microscopic parameters. METHODS: Placentas where villitis was observed, were obtained from the pathology database from January 2013 to June 2018. VUE was graded as low grade (LG), high grade (HG) and basal villitis (BV) and subcategorized based on extent and cell type. Its association with selected maternal, neonatal and placental parameters was evaluated. RESULTS: A total of 1603 placentas were received and 163 singleton placentas with villitis (10%) were reported. LG and HG villitis was observed in 58% and 25% cases respectively. Basal villitis was seen in 24% and pure basal villitis without involvement of parenchymal villi was seen in 16.6%. While there was near equal distribution of focal (n = 45) and multifocal (n = 50) LG villitis, diffuse HG villitis (n = 32) was more common than patchy HG villitis (n = 9). Overall villitis was more common in preterm pregnancies (59.5%) with most of them being basal villitis and low-grade villitis (64.2%, p value .029). None of the other maternal and neonatal parameters had any significance. Placental dimensions (length and breadth) showed a significant negative association with VUE, especially high-grade and multifocal low-grade villitis. CONCLUSION: VUE was a common finding in preterm births and its novel association with placental size opens avenues for further research on alternative mechanisms involved in the association between villitis, placental function and adverse pregnancy outcomes.

Expression of HER2 and EGFR Proteins in Advanced Stage High-grade Serous Ovarian Tumors Show Mutual Exclusivity.

Human epidermal growth factors play an important role in ovarian carcinogenesis and are evaluated for prognostic and possible therapeutic roles in high-grade serous ovarian malignancies. The present study was undertaken to evaluate the expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) in advanced stage serous carcinoma and their influence on prognosis. The expression of HER2 and EGFR was studied in 59 cases of stage III and IV ovarian serous carcinomas by immunohistochemistry and fluorescent in situ hybridization. Of the 48 interpretable tumors for HER2, 6 tumors (12.5%) were scored as positive, 14 (29%) as equivocal and 28 tumors (58.5%) were negative by immunohistochemistry, while only 2/48 (4%) showed frank amplification by fluorescent in situ hybridization with ≥4 copies per cell. HER2 gene expression measured by quantitative polymerase chain reaction had good positive correlation with both protein expression and gene amplification. Although EGFR expression was seen in 32% of tumors, none of the tumors positive for HER2 protein or gene amplification had co-expression of EGFR indicating mutual exclusivity of their expression. Gene expression of both proteins also confirmed their inverse correlation (Pearsons CC=-0.15, P=0.3). Further there was no influence of protein or gene expression of these markers on the overall survival. In conclusion, HER2 and EGFR are expressed in a small percentage of tumors and the mutual exclusivity of these markers precludes the possibility of dual targeting with anti-HER2 and anti-EGFR therapy in advanced stage high-grade serous ovarian carcinoma.

Assessment of cytological features of glandular lesions of the cervix on conventional smear preparations-a comprehensive study from a tertiary care hospital.

BACKGROUND: Atypical glandular cells (AGC) as a diagnostic category in cervicovaginal cytology remains as a challenge to cytopathologists. AIMS: The aim of the present study is to identify the cytological features helpful in categorizing AGC as reactive or neoplastic upon correlation with histology. MATERIALS AND METHODS: The study was a retrospective review of cervical smears, with histopathological follow up, reported as glandular lesions for a period of 9 years. The architectural and nuclear features studied were adapted from The Bethesda System (TBS) to stratify the lesions as AGC, AGC-FN (atypical glandular cells favour neoplasia) and adenocarcinoma. The cytological categories were correlated with histology. RESULTS: A total of 89 cases of which 67 (AGC NOS = 34, AGC FN = 19, adenocarcinoma = 14) with histology were reviewed. Neoplastic lesions were encountered in 14 cases (34.6%). Of the cases diagnosed as AGC-NOS, AGC-FN and adenocarcinoma, 26.5%, 68.4% and 100% respectively were neoplastic on histopathology. Squamous lesions accounted for 14.9% of all the glandular lesions. Rosette or acinar formation and loss of polarity frequently observed in neoplastic lesions as compared to reactive changes (p = 0.0004, p = 0.001). Of the nuclear features, nuclear hyperchromasia or coarse clumping of chromatin along with nuclear membrane irregularity and nuclear pleomorphism was frequently associated with neoplastic lesions as compared to reactive conditions (p = 0.007, p = 0.001, p = 0.0002). CONCLUSION: A diagnosis of AGC at cytology harbors significant number of malignant lesions when confirmed on biopsy. Architectural features complemented with nuclear characteristics helps in differentiating between reactive and neoplastic conditions. Hence stratifying glandular lesions at cytology according to TBS helps in the management.

A 51-Year-Old Woman With Pellets in the Sputum.

CASE PRESENTATION: A 51-year-old woman with no comorbidities presented with a 3-month history of cough with mucopurulent expectoration and intermittent fever. Over the past 1 month, she complained of streaky hemoptysis and gave history of expectorating "whitish pellets" in the sputum on two occasions. She had developed progressive breathlessness for a week prior to presentation to our hospital. There was no history of chest pain or loss of weight or appetite. She was a nonsmoker and did not consume alcohol. She had received multiple courses of antibiotics at another center with no relief of symptoms.

Placental expression of angiogenesis-related genes and their receptors in IUGR pregnancies: correlation with fetoplacental and maternal parameters.

Objectives: Aberrations in placental vascular development compromising fetal supply of oxygen and essential nutrients can be a significant contributor to intrauterine growth restriction (IUGR). The development of placental vascular tree is under the influence of two families of growth factors, namely the vascular endothelial growth factor (VEGF) family and angiopoietin/TEK family. In this study, we have examined the expression of angiogenesis-related growth factors, mainly VEGF family and angiopoietin-TEK (endothelial-specific receptor tyrosine kinase) family genes in placentae from IUGR pregnancies uncomplicated by preeclampsia (PE) compared to normal pregnancies.Methods: Placentae from normotensive IUGR (n = 42) and appropriate for gestational age (AGA) pregnancies (n = 47) were collected and examined histologically. Clinical parameters were obtained from the medical records. Real-time quantitative PCR was performed to assess placental transcript abundance of VEGF, PGF, FLT1, ANGPT1, ANGPT2, and TEK normalized to a panel of reference genes. Associations of placental transcript abundance of the genes with maternal, placental, and neonatal parameters were tested.Results: Placental transcript abundance for VEGF (relative expression 10.81 versus 12.98, p < .001), PGF (12.14 versus 13.8, p < .001) and ANGPT2 (3.67 versus 9.55, p = .002) were significantly lower in IUGR placentae compared to AGA. The transcript level of VEGF showed significant negative correlation with birth weight (r = -0.419, p = .006), placental weight (r = -0.318, p = .040), placental length (r = -0.389, p = .011) and breadth (r = -0.308, p = .047) only in the IUGR group. Presence of histopathological features of hypoxia correlated with significantly higher transcript levels of PGF in IUGR placentae (12.6 versus 10.9, p = .046).Conclusion: The low levels of VEGF transcripts may be responsible for the impaired angiogenesis in IUGR placentae. The significance of higher relative expression of PGF in the presence of chronic hypoxia needs to be explored.

Do Doppler Changes Reflect Pathology of Placental Vascular Lesions in IUGR Pregnancies?

OBJECTIVES: Doppler assessment of uteroplacental (UP) and fetoplacental (FP) circulation detects abnormal waveforms in intrauterine growth-restricted (IUGR) pregnancies. Similarly, histopathology also reveals lesions of vascular compromise in IUGR placenta. We evaluated an association between Doppler and histopathological (HP) assessment of the maternal and fetal circulation in IUGR. METHODS: IUGR cases with both Doppler and histopathology assessment were selected from our database. Doppler patterns recorded UP and FP insufficiency. The HP vascular lesions were classified as maternal vascular underperfusion and fetal thrombotic vasculopathy (FTV). IUGRs were grouped based on (i) presence of preeclampsia (PE), (ii) clinical onset (early vs late) of IUGR (early onset [EO]/late onset), and (iii) gestational age (term, T/preterm, PT). RESULTS: Abnormal Doppler waveforms were present in 69 of the total 88 IUGR cases (78.4%). The most frequent pattern was fetoplacental insufficiency (FPI) (66%) which was combined with uteroplacental insufficiency (UPI) in 49%. HP showed vascular lesions in 52.3% and most frequent was FTV (38%). PE-associated IUGR (n = 49) had higher UPI pattern (75.5% vs 43.6%, P = .004), while normotensive IUGR had higher FPI pattern (28.2% vs 8.2%, P = .01). EO-IUGR (n = 55) and PT-IUGR (n = 52) had significant abnormal Doppler waveforms (P < .05) with higher combined patterns and brain sparing. Doppler was more sensitive for fetal vascular lesions than maternal (75.8% vs 66.7%). However, 42% of cases with normal Doppler findings showed HP vascular lesions. CONCLUSION: IUGR pregnancies harbor significant vascular compromise. Fetal circulatory lesions were more common in IUGR pregnancies. In a significant number of cases with normal Doppler report, vascular lesions were identified on histopathology, emphasizing placental examination in all cases of IUGR.

CD15 as a marker of fetoplacental endothelial immaturity in IUGR placentas.

BACKGROUND: Structural or functional defects in the placenta, are the primary cause of growth restriction of the fetus. Morphological examination of such placentas from intrauterine growth restricted (IUGR) fetuses often appears deceptively normal. Evaluation of angiogenesis and fetoplacental vasculature is critical to understand the underlying pathogenesis of fetal growth restriction in both idiopathic as well as cases where it is thought to be secondary to complications like preeclampsia (PE). We analyzed the immaturity of fetoplacental vasculature using CD15, which is a stage specific embryonic antigen known to be expressed in immature endothelium. MATERIAL AND METHODS: One hundred and twelve placentas (81 from IUGR and 31 from gestationally appropriate samples (appropriate for gestational age (AGA)) were collected based on stringent inclusion criteria, and subjected to detailed examination of morphology and microscopy along with immunostaining for CD15. IUGR placentas known to have villous immaturity such as those associated with gestational diabetes, Rh negative pregnancies and anemia were excluded. The time of clinical onset of IUGR, associated complications like PE and oligohydramnios along with clinical variables were recorded. CD15 expression was scored in both distal and proximal vasculature and the values in IUGR and AGA pregnancies were compared and correlated with clinical variables. RESULTS: The mean CD 15 scores in both proximal vasculature (PV) as well as distal (DV) vasculature were significantly higher in the IUGR group compared to AGA (17.7 versus 5.16 in PV and 50.8 versus 23.7 in distal vasculature (DV)). Gestational age had no influence on CD15 staining in PV or DV in IUGR group, whereas preterm AGAs expressed higher CD15 only in the distal vessels. PE, oligohydramnios and the time of onset of IUGR did not influence the fetal vascular immaturity, as measured by CD15 scores. Although none of the clinical or obstetric factors influenced CD15 staining in AGA, fetal vessel immaturity in the IUGR group remained high even after adjusting for confounding variables like maternal age, gestational age and birth weight. Histological features suggestive of chronic hypoxia were significantly higher in IUGR placentas, compared to AGA and correlated positively with CD15 expression. CONCLUSION: Fetoplacental endothelium in both PV and DV is immature in IUGR irrespective of the gestational age or any other associated factors and CD15 immunodetection is a valuable marker for assessment of immaturity.

Placenta in intrauterine fetal demise (IUFD): a comprehensive study from a tertiary care hospital.

Background: Intrauterine fetal demise (IUFD) is an unpredictable and challenging obstetric complication. Its etiology is multifactorial with more than 60% attributed to the placental cause. The present study was done with a primary objective of understanding the placental lesions underlying IUFD. Methods: In this retrospective observational study, IUFD cases (>22 weeks) between January 2012 and September 2015 were collected from pathology database. The clinical details with ultrasound findings were collected from mother's charts. The lesions were classified into (A) maternal vascular malperfusion (MVM) including retroplacental hematomas, (B) fetal vascular malperfusion (FVM), (C) inflammatory lesions, and (D) idiopathic. The contributor to fetal death was classified as direct, major, minor, unlikely, or unknown. Placental findings of fetal hypoxia were recorded. Results: The study included 100 cases of IUFD. The mean maternal age was 26 years (18-36 years). Primipara were 46. There were 65 early preterm (PT) (<34 weeks), 20 late PT (34 weeks to <37 weeks) and 15 term (>37 weeks) IUFD. The mean gestation age was 30 weeks. The ratio of male:female fetuses was 1:1.7. Relevant obstetric complications included preeclampsia (n = 39), intrauterine growth restriction (IUGR) (n = 7), pre-gestational diabetes (n = 7), bad obstetric history (n = 6), oligohydramnios (n = 5). The mean placental weight was 256 g. Maternal vascular malperfusion had the highest incidence (30%), followed by combined maternal and FVM (10%). Exclusive inflammatory lesions and FVM were seen in 12 and 6%, respectively. No cause was identified in 18%. Direct contributor to IUFD was identified in 51 cases and major, minor, unlikely contribution in 21, 11 and nine cases, respectively. In nine cases, it was unknown. Lesions indicating fetal hypoxia were noted in 35 cases. In both early and late PT, MVM featured more commonly (23 and 5%). In term placentas, the most common cause was idiopathic. Conclusions: Lesions of MVM were the most common cause of IUFD and served as a direct contributor to fetal demise.

Combined Vitamin B-12 and Balanced Protein-Energy Supplementation Affect Homocysteine Remethylation in the Methionine Cycle in Pregnant South Indian Women of Low Vitamin B-12 Status.

Background: Low-quality dietary protein intake and vitamin B-12 deficiency could interact to decrease methionine transmethylation and remethylation rates during pregnancy and may affect epigenetic modifications of the fetal genome.Objective: The objective of this randomized, partially open-labeled intervention trial was to examine the effect of supplemental high-quality protein and vitamin B-12 on third-trimester methionine kinetics in pregnant Indian women with a low vitamin B-12 status.Methods: Pregnant women with low serum vitamin B-12 concentrations (<200 pmol/L) were randomly assigned to 1 of 3 groups: the first group received balanced protein-energy supplementation of 500 mL milk/d plus a 10-µg vitamin B-12 tablet/d (M+B-12 group; n = 30), the second group received milk (500 mL/d) plus a placebo tablet (M+P group; n = 30), and the third group received a placebo tablet alone (P group; n = 33). Third-trimester fasting plasma amino acid kinetics were measured by infusing 1-13C,methyl-2H3-methionine, ring-2H5-phenylalanine, ring-2H4-tyrosine,1-13C-glycine, and 2,3,3-2H3,15N-serine in a subset of participants. Placental mRNA expression of genes involved in methionine pathways, placental long interspersed nuclear elements 1 (LINE-1) methylation, and promoter methylation levels of vascular endothelial growth factor (VEGF) were analyzed.Results: Remethylation rates in the M+B-12, M+P, and P groups were 5.1 ± 1.7, 4.1 ± 1.0, and, 5.0 ± 1.4 µmol ⋅ kg-1 ⋅ h-1, respectively (P = 0.057), such that the percentage of transmethylation remethylated to methionine tended to be higher in the M+B-12 group (49.5% ± 10.5%) than in the M+P group (42.3% ± 8.4%; P = 0.053) but neither differed from the P group (44.2% ± 8.1%; P > 0.1). Placental mRNA expression, LINE-1, and VEGF promoter methylation did not differ between groups.Conclusions: Combined vitamin B-12 and balanced protein-energy supplementation increased the homocysteine remethylation rate in late pregnancy. Thus, vitamin B-12 along with balanced protein-energy supplementation is critical for optimal functioning of the methionine cycle in the third trimester of pregnancy in Indian women with low serum vitamin B-12 in early pregnancy. This trial was registered at clinicaltrials.gov as CTRI/2016/01/006578.

"The Jelly Belly": Diagnostic Dilemmas and Current Concepts.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare and poorly understood clinicopathological entity characterized by gelatinous ascites with neoplastic or non-neoplastic mucinous implants in the peritoneum. Although its origin was debated, current evidence in literature favours the appendix as the origin of the disease, over the ovaries. The changing terminologies in the classification of this entity pose diagnostic and management challenges. CASE REPORTS: Herein, we report three cases of PMP in postmenopausal women, their clinical presentation, pathological staging based on the peritoneal tumor deposits and the treatment administered. Two patients recovered uneventfully, while one had recurrence of adenocarcinoma. CONCLUSION: The rarity of this disease and the diagnostic challenges associated with it are discussed with an emphasis on the current concepts in its origin and management. Appropriate classification and complete removal of the tumor is mandated to prevent disease-related mortality.

Crystalloids in submandibular sialadenitis.

Fine needle aspiration cytology of the salivary glands plays an important role in the diagnosis of neoplastic and non neoplastic lesions of salivary gland. Crystalloids in salivary gland lesions are a rare occurrence. A case of submandibular sialomegaly in an elderly patient with a clinical suspicion of metastasis was subjected to FNAC which showed crystalloids morphologically resembling amylase occurring in a background of sialadenitis. These crystals are non birefrigent, eosinophilic structures with a variety of geometric shapes including needles, rods, rectangular structures that do not stain with mucin stains. Other important crystalloids which can be observed in neoplastic and non-neoplastic salivary gland lesions are tyrosine-rich crystalloids, collagenous crystalloids, and oxalate crystals. These can be distinguished both morphologically and on the basis of several staining techniques in addition to biochemical studies. FNAC plays a major role in the diagnosis of these lesions and helps in avoiding unnecessary surgery.

How accurate is intraoperative frozen section in the diagnosis of ovarian tumors?

AIM: The aim of this study was to evaluate the accuracy of intraoperative frozen section of ovarian tumors and to analyze the factors that influence the accuracy. MATERIAL AND METHODS: We compared the frozen section diagnosis of 218 ovarian tumors with their final diagnosis in paraffin sections, over a period of 10 years from 1999 to 2008. RESULTS: Results were analyzed on two parameters: (i) status of malignancy and (ii) histological type. The overall accuracy was 95%. The sensitivity for benign, borderline and malignant tumors was 99.3%, 86.66% and 96.3%, respectively. The corresponding specificities were 92.6%, 97% and 100%. Most of the discrepant cases were of borderline category. The overall accuracy for histological diagnosis was 80.7%. The number of sections examined at frozen and paraffin had a statistically significant association with the accuracy of frozen section. CONCLUSION: Frozen section diagnosis is of high quality at our center with a few exceptions in borderline category. The numbers of sections examined have a statistically significant influence on the accuracy of frozen section of ovarian masses.

A study of pelvic and para-aortic lymph node involvement in surgically staged endometrioid carcinoma of endometrium.

PURPOSE: The purpose of this study was to investigate the influence of the depth of myometrial invasion and tumor grade on lymph node involvement in endometrial carcinoma. METHODS: Patients with endometrioid carcinoma of endometrium who underwent surgical staging between January 1999 and September 2010 under the division of gynecologic oncology were studied retrospectively. Patients treated by radiotherapy or chemotherapy before surgeries were excluded. RESULTS: The study group included 61 patients. Six patients had lymph node metastasis, of which 83.3 % had >50 % myometrial invasion (P = 0.052). Grades 1, 2, and 3 were each seen in 33.3 % of them (P = 0.061). When the study group was divided into two sets, namely, those with <50 and >50 % myometrial invasion, the odds ratio was 10.3, which means that the chance of the prevalence of lymph node metastasis in the latter group is 10 times more. CONCLUSIONS: Although the P value was not significant, the odds ratio reveals that there is an increased risk of lymph node positivity with deeper myometrial invasion. Surgical staging needs to be done for all operable cases of carcinoma endometrium to determine the prognosis and further management.

Vascular endothelial growth factor expression in ovarian serous carcinomas and its effect on tumor proliferation.

INTRODUCTION: Vascular endothelial growth factor (VEGF), an endothelial mitogen, acts through VEGF receptors (VEGFRs) on the endothelial cells. During neoplastic transformation, it is hypothesized that the tumor expresses VEGF and also acquire VEGF receptor, enabling VEGF action in an autocrine and paracrine manner with varied effects on the tumor growth and progression. This study on ovarian serous carcinomas (OSCs) was done to determine the expression of VEGF and to correlate it with tumor proliferation. MATERIAL AND METHODS: Forty cases of OSCs were included. Immunohistochemistry was performed for VEGF and Ki-67. The VEGF slides were assigned an immunohistochemical score based on the staining intensity (a) and the percentage of tumor cells staining (b). The sum of both (a) and (b) ranged from 0-6. VEGF was considered positive when the score was more than 2. For Ki-67, maximally immunostained areas were selected; 500 cells counted and positive fraction determined. Mann Whitney test was used to determine the difference in the median value of Ki-67 between VEGF positive tumors and VEGF negative tumors. RESULTS: Of the 40 cases, 32 cases had a VEGF score of >2 (positive) and 8 cases had VEGF score <2 (negative). The Ki-67 score ranged from 2-98%, with mean of 51%. The median Ki-67 index was much higher in VEGF positive cases as compared to VEGF negative tumors (57.5% vs. 40%). However, the difference in the two categories did not reach statistical significance (P = 0.45, Mann Whitney test). CONCLUSION: Ovarian serous carcinomas express VEGF in a significant number of cases (80% in the present study) although its potential mitogenic effect on tumor cells was not confirmed.