Belzutifan for von Hippel-Lindau Disease: Pancreatic Lesion Population of the Phase 2 LITESPARK-004 Study.

PURPOSE: Primary analysis of the ongoing, single-arm, phase 2 LITESPARK-004 study (NCT03401788) showed clinically meaningful antitumor activity in von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC) and other neoplasms with belzutifan treatment. We describe results of belzutifan treatment for VHL disease-associated pancreatic lesions [pancreatic neuroendocrine tumors (pNET) and serous cystadenomas]. PATIENTS AND METHODS: Adults with VHL diagnosis based on germline VHL alteration, ≥1 measurable RCC tumor, no renal tumor >3 cm or other VHL neoplasm requiring immediate surgery, Eastern Cooperative Oncology Group performance status of 0 or 1, and no prior systemic anticancer treatment received belzutifan 120 mg once daily. End points included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and linear growth rate (LGR) in all pancreatic lesions and pNETs per RECIST version 1.1 by independent review committee, and safety. RESULTS: All 61 enrolled patients (100%) had ≥1 pancreatic lesion and 22 (36%) had ≥1 pNET measurable at baseline. Median follow-up was 37.8 months (range, 36.1-46.1). ORR was 84% [51/61; 17 complete responses (CR)] in pancreatic lesions and 91% (20/22; 7 CRs) in pNETs. Median DOR and median PFS were not reached in pancreatic lesions or pNETs. After starting treatment, median LGR for pNETs was -4.2 mm per year (range, -7.9 to -0.8). Eleven patients (18%) had ≥1 grade 3 treatment-related adverse event (AE). No grade 4 or 5 treatment-related AEs occurred. CONCLUSIONS: Belzutifan continued to show robust activity and manageable safety in VHL disease-associated pNETs.

Quantitative Multiplex Immunofluorescence Evaluation of the Tumor Microenvironment in Pretreatment Tumors of Patients with Metastatic Breast Cancer and Serous Ovarian Carcinoma Treated with Liposomal Eribulin.

Eribulin inhibits microtubule polymerization and suppresses epithelial-mesenchymal transition. Conventional pathology approaches have not identified a precise predictive biomarker for Eribulin. We performed qmIF on pre-treatment tissue from 11 patients (6 TNBC, 5 HGSOC) treated with Eribulin-LF. T-lymphocytes were the dominant immune-subset in TME, with higher levels detected in stroma vs tumor (9% vs 2%). Greater density of CD3+ (p = 0.01) and CD3 + CD8+ (p = 0.03) cells and closer proximity between CD3 + CD8+ and tumor cells was observed in the patients with disease control (PR + SD) vs. progressive disease. QmIF identified an association between TIL infiltration and Eribulin-LF sensitivity, which should be evaluated further in prospective studies.

Short-term organoid culture for drug sensitivity testing of high-grade serous carcinoma.

OBJECTIVE: Cancer patient-derived organoids (PDOs) grow as three dimensional (3D) structures in the presence of extracellular matrix and have been found to represent the original tumor's genetic complexity. In addition, PDOs can be grown and subjected to drug sensitivity testing in a shorter time course and with lesser expense than patient-derived xenograft models. Many patients with recurrent ovarian cancer develop malignant effusions that become refractory to chemotherapy. Since these same patients often present for palliative aspiration of ascites or pleural effusions, there is a potential opportunity to obtain tumor specimens in the form of multicellular spheroids (MCS) present in malignant effusion fluids. Our objective was to develop a short duration culture of MCS from ovarian cancer malignant effusions in conditions selected to support organoid growth and use them as a platform for empirical drug sensitivity testing. METHODS: In this study, malignant effusion specimens were collected from patients with high-grade serous ovarian carcinoma (HGSOC). MCS were recovered and subjected to culture conditions designed to support organoid growth. In a subset of specimens, RNA-sequencing was performed at two time points during the short-term culture to determine changes in transcriptome in response to culture conditions. Organoid induction was also characterized in these specimens using Ki67 staining and histologic analysis. Drug sensitivity testing was performed on all specimens. RESULTS: Our model describes organoids formed within days of primary culture, which can recapitulate the histological features of malignant ascites fluid and can be expanded for at least 6 days. RNA-seq analysis of four patient specimens showed that within 6 days of culture, there was significant up-regulation of genes related to cellular proliferation, epithelial-mesenchymal transition, and KRAS signaling pathways. Drug sensitivity testing identified several agents with therapeutic potential. CONCLUSIONS: Short duration organoid culture of MCS from HGSOC malignant effusions can be used as a platform for empiric drug sensitivity testing. These ex vivo models may be helpful in screening new or existing therapeutic agents prior to individualized treatment options.

Outcome-Related Differences in Gene Expression Profiles of High-Grade Serous Ovarian Cancers Following Neoadjuvant Chemotherapy.

Large-scale genomic studies have detailed the molecular landscape of tumors from patients with high-grade serous ovarian cancers (HGSC) who underwent primary debulking surgery and correlated the identified subgroups to survival. In recent years, there is increased use of neoadjuvant chemotherapy (NACT) for patients with HGSC and while abundant data exist for patients who underwent primary debulking, little data are available on the cancer cells remaining after NACT that could lead to recurrences. We aimed to analyze gene expression profiles of NACT-treated HGSC tumor samples, and correlate them to treatment response and outcome. Tumor samples were collected from patients with stage III or IV HGSC (NACT cohort, N = 57) at the time of surgery and diagnosis (biopsy samples N = 8). Tumor content was validated by histologic examination and bioinformatics. Gene expression analysis was performed using a tailored NanoString-based assay, while sequencing was performed using MiSeq. A cross-validated survival classifier revealed patient clusters with either a "Better" or "Worse" prognostic outcome. The association with overall survival remained significant after controlling for clinical variables, and differential gene expression, gene set enrichment analyses, and the appropriate survival models were used to assess the associations between alterations in gene expression in cancer cells remaining after NACT and outcome. Pathway-based analysis of the differentially expressed genes revealed comparatively high levels of cell cycle and DNA repair gene expression in the poor outcome group. IMPLICATIONS: Our work suggests mRNA expression patterns in key genes following NACT may reflect response to treatment and outcome in patient with HGSC.

Reannotation and Analysis of Clinical and Chemotherapy Outcomes in the Ovarian Data Set From The Cancer Genome Atlas.

PURPOSE: The ovarian cancer data set from The Cancer Genome Atlas integrates genomic and proteomic data with clinical annotations based on chart abstractions. We aimed to develop an algorithm to create a matching, more accessible clinical data set cataloging time to treatment failure (TTF) of sequential lines of treatment in patients with serous ovarian cancers. MATERIALS AND METHODS: The master data set of 587 patients with serous ovarian cancer was condensed into a more homogeneous and clinically relevant population comprised of high-risk patients with both grade 3 cancers and stage III or IV disease, resulting in a subgroup of 450 patients. We quantified the TTF of different lines of therapy as well as different therapeutic combinations by extrapolating from the time of starting one therapy to the time of starting a subsequent therapy. RESULTS: The overall survival (OS) of patients was highly related to platinum sensitivity status, with median OS times of 56.6, 27.0, and 11.6 months in patients who had platinum-sensitive, -resistant, or -refractory disease, respectively. In high-risk patients, the median TTFs were 14.8, 10.2, 5.7, and 4.1 months with the first, second, third, and fourth lines of chemotherapy, respectively. Patients with stable disease after first-line therapy had similar OS outcomes as patients with partial remissions (34.4 v 33.7 months, respectively). CONCLUSION: This new data set enhances the clinical annotation by providing exploitable chemotherapy benefit data that can now be paired with genomic and proteomic data within The Cancer Genome Atlas data. The major determinant of OS in this study was platinum sensitivity status. TTF decreased with each successive line of therapy. However, patients who achieved only stable disease with first-line therapy had OS similar to those with partial remission.

[Effectiveness of Carboplatin plus Taxane Chemotherapy for Advanced or Recurrent Uterine Serous Carcinoma].

OBJECTIVE: Uterine serous carcinoma(USC)is more aggressive compared to endometrioid adenocarcinoma, and often exhibits intraperitoneal spread, resulting in a poor prognosis. It is a rare subtype of uterine cancers, accounting for 5%of cases in Japan; therefore, optimal chemotherapy regimens for patients with advanced or recurrent disease have not been established. In the present study, we evaluated the safety and efficacy of carboplatin plus taxane chemotherapy for the treatment of patients withadvanced and recurrent USC. METHODS: Patients withmeasurable advanced or recurrent USC who underwent carboplatin plus taxane chemotherapy, and in whom toxicities could be evaluated were eligible. Carboplatin(AUC 5)and paclitaxel(180mg/m2)were administered on day 1 of a 3-week cycle. Patients who required dose adjustments or carboplatin plus docetaxel because of age, comorbidities, or adverse events were included. RESULTS: Nine patients were included. The median patient age was 68 years(range, 45-81 years). Seven patients had Stage IV B disease(5 withperitoneal dissemination, 1 withbone metastasis, and 1 withmultiple lymphnode metastases, including metastasis at the mediastinal lymph nodes), and 2 patients had recurrent disease, both of whom developed postoperative peritoneal recurrence. One patient achieved a complete response(CR), and 6 achieved a partial response(PR), witha response rate(CR+PR)of 78%. Th e2 patients with recurrent disease achieved a PR. The median progression-free survival for the 7 responders was 9 months (range, 2-90 months). In terms of hematological toxicities, GradeB3 neutropenia occurred in 7 patients, but febrile neutropenia did not occur. One patient developed sepsis because of a subcutaneous central venous port infection. CONCLUSION: TC was a safe and efficacious regimen for patients with advanced or recurrent USC. To validate these findings, further investigations in a larger patient population are warranted.

Ridaforolimus improves the anti-tumor activity of dual HER2 blockade in uterine serous carcinoma in vivo models with HER2 gene amplification and PIK3CA mutation.

OBJECTIVE: Uterine serous carcinomas (USC) harbor simultaneous HER2 (ERBB2) over-expression and gain of function mutations in PIK3CA. These concurrent alterations may uncouple single agent anti-HER2 therapeutic efficacy making inhibition of the mammalian target of rapamycin (mTOR) a promising option to heighten anti-tumor response. METHODS: Both in vitro and in vivo experiments were conducted to assess proliferation, cell death and anti-tumor activity of ridaforolimus, lapatinib and combination lapatinib, trastuzumab (L/T) and ridaforolimus. With institutional approval, NOD/SCID mice bearing xenografts of non-immortalized, HER2 gene amplified cell lines (ARK1, ARK2) with and without PIK3CA gene mutations were divided into four arm cohorts. Ridaforolimus was administered alone and in combination with L/T. Tumor volumes were assessed and posttreatment analysis was performed. RESULTS: We observed dose dependent in vitro abrogation of downstream target proteins including phospho-AKT and phospho-S6. In both in vivo models, single agent ridaforolimus impaired xenograft tumor growth. Combination ridaforolimus and L/T, however, further improved the observed anti-tumor activity only in the ARK1 model with the PIK3CA gene mutation (E542K). The addition of mTOR inhibition to dual HER2 blockade added no additional anti-tumor effects in the ARK2 xenografts. Western blot and immunohistochemical analysis of downstream pathway alterations following in vivo treatment revealed dual HER2 blockade with ridaforolimus was necessary to induce apoptosis, decrease proliferation and abrogate phospho-S6 protein expression in the PIK3CA mutated model. CONCLUSIONS: These pilot data suggest that PIK3CA gene mutation may be an effective biomarker for selecting those HER2 over-expressing USC tumors most likely to benefit from mTOR inhibition.

IMP3 as a cytoplasmic biomarker for early serous tubal carcinogenesis.

BACKGROUND: Serous tubal intraepithelial carcinoma (STIC) and the p53 signature in tubal mucosa have been supported to be precursor lesions in high-grade serous carcinoma (HGSC) of the fallopian tube, ovary, and peritoneum. It remains critical to find biomarkers for precursor lesions in order to detect HGSCs efficiently. IMP3 is an oncoprotein that has been explored in human malignancies. No studies have specifically addressed the expression of IMP3 in precursor or early lesions of HGSC. The main purposes of this study are to evaluate if IMP3 plays any role in the process of pelvic serous carcinogenesis by examining its expression in HGSC precursor lesions, to examine the relationship between IMP3 and p53 in those precursor lesions, and to check if IMP3 can be used as a biomarker for early diagnosis. METHODS: Immunohistochemistry for IMP3 and p53 was performed and evaluated in 48 HGSCs with STIC, 62 HGSCs without STIC, and 60 benign cases as negative controls. Sections of fallopian tubes with or without STIC , as well as cancers within the ovaries, were studied. IMP3 signature was defined as strong IMP3 cytoplasmic staining in 10 or more consecutive benign-looking tubal epithelial cells. The relationship between IMP3 and p53 overexpression was examined. RESULTS: In the 48 HGSC patients with STIC, IMP3 was positive in 46% of STIC lesions and had a similar positive rate in the invasive components of HGSC. IMP3 was also expressed in normal appearing tubal epithelia (IMP3 signature) in 15 (31%) of 48 HGSC cases with STIC and 10 (16%) of 62 cases without STIC. In contrast, no single IMP3 signature was found in the benign control group. Concordant expression of IMP3 and p53 signatures in the STIC group was found in up to one-third of the cases. There were also five (10%) STIC cases with positive IMP3 and negative p53. CONCLUSIONS: We conclude that IMP3 may be involved in the process and progression of pelvic HGSC and may serve as a complimentary biomarker in diagnosing STIC.

The PI3K/mTOR dual inhibitor NVP-BEZ235 reduces the growth of ovarian clear cell carcinoma.

Patients with clear cell carcinoma of the ovary (OCCC) have poor survival due to resistance to standard chemotherapy. OCCC has frequent activating mutations of the PIK3CA gene. The present study was conducted to clarify the efficacy of the inhibition of the PI3K-AKT-mTOR pathway in OCCC. We used 8 OCCC cell lines and 5 ovarian serous adenocarcinoma (OSAC) cell lines. The mutation status of the PIK3CA and KRAS genes was examined by direct sequencing. The IC50 values of NVP-BEZ235 (BEZ235) and temsirolimus were determined by WST-8 assay. Protein expression levels of PI3K-AKT-mTOR pathway molecules were examined by western blotting. Cell cycle distribution was analyzed by flow cytometry. Annexin V staining was used for detecting apoptosis. We also investigated the effects of BEZ235 on OCCC tumor growth in a nude mouse xenograft model. Four of the 8 OCCC cell lines showed a PIK3CA mutation while none of the 5 OSAC cell lines showed a mutation. The IC50 values of BEZ235 for the OCCC cell lines were lower than these values for the OSAC cell lines. The IC50 value of temsirolimus was higher than BEZ235 in the OCCC cell lines. The PIK3CA mutation was more frequently noted in OCCC than OSAC cells, but the sensitivity of these cell lines to BEZ235 or temsirolimus was not related to the mutation status. pHER3 and pAkt proteins were expressed more frequently in OCCC compared with OSAC. However, protein expression levels were distributed widely, and were not related to the sensitivity. Treatment with BEZ235 suppressed expression of pAkt, although treatment with temsirolimus did not. OCCC cells exhibited G1 phase arrest after treatment with BEZ235 and apoptosis with a higher concentration of the agent. BEZ235 significantly inhibited tumor growth in mice bearing OVISE and TU-OC-1 cell tumors. The present study indicated that the PI3K-AKT-mTOR pathway is a potential target for OCCC, and that BEZ235 warrants investigation as a therapeutic agent.

Death domain-associated protein DAXX promotes ovarian cancer development and chemoresistance.

BACKGROUND: The role of DAXX in ovarian cancer development and metastasis has not been investigated before now. RESULTS: Overexpression of DAXX enhanced ovarian cancer cell proliferation, colony formation, and migration, whereas Daxx depletion had the opposite effects. CONCLUSION: DAXX promotes ovarian cancer cell proliferation and chemoresistance. SIGNIFICANCE: ModulatingDAXXmay be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers. Understanding the genes involved in apoptosis and DNA damage responses may improve therapeutic strategies for ovarian cancer. The death domain-associated protein DAXX can be either a pro-apoptotic or an anti-apoptotic factor, depending on the cell type and context. In this study, we found that DAXX was highly expressed in human ovarian surface epithelial tumors but not in granulosa cell tumors. In cultured ovarian cancer cells, DAXX interacted with promyelocytic leukemia protein (PML) and localized to subnuclear domains (so-called PML nuclear bodies). A role for DAXX in ovarian cancer cell proliferation, metastasis, and radio/chemoresistance was examined. Overexpression of DAXX enhanced multiple ovarian cancer cell lines' proliferation, colony formation, and migration, whereas Daxx depletion by RNA interference had the opposite effects. When transplanted into nude mice, ovarian cancer cells that overexpressed DAXX displayed enhanced tumorigenesis capability in vivo, whereas Daxx depletion inhibited tumor development. Importantly, Daxx induced tumorigenic transformation of normal ovarian surface epithelial cells. Daxx also protected ovarian cancer cells against x-irradiation- and chemotherapy-induced DNA damage by interacting with PML. Taken together, our results suggest that DAXX is a novel ovarian cancer oncogene that promotes ovarian cancer cell proliferation and chemoresistance in ovarian cancer cells. Thus, modulating DAXX-PML nuclear body activity may be an effective strategy for preventing the recurrence and chemoresistance of ovarian cancers.

Molecular abnormalities in ovarian carcinoma: clinical, morphological and therapeutic correlates.

The histopathological classification of ovarian surface epithelial carcinomas (referred to hereafter as 'ovarian carcinoma') has shifted over the past 10 years to reflect more clearly our understanding of molecular events during carcinogenesis. Ovarian carcinoma is no longer viewed as a single entity but as multiple disease processes, with each having different molecular pathways altered during oncogenesis, resulting in differences in clinical and pathological features, such as biomarker expression, pattern of spread and response to chemotherapy. There are five subtypes of ovarian carcinoma that are sufficiently distinct and well-characterized that they should be considered to be different diseases, i.e. high-grade serous, clear cell, endometrioid, mucinous and low-grade serous, from most to least common, respectively. This review summarizes the molecular abnormalities of these five ovarian carcinoma subtypes, relating them to clinical and pathological features.

Micropapillary pattern in serous borderline ovarian tumors: does it matter?

OBJECTIVE: To evaluate the clinical and prognostic impact of micropapillary pattern in patients with serous borderline ovarian tumors (SBOT). METHODS: We retrospectively assessed 130 consecutive patients with typical (n=97, 74.6%) or micropapillary (n=33, 25.4%) SBOT. Clinicopathologic factors and outcomes were compared between these two groups. RESULTS: There were no significant between-group differences in age, menopausal status, parity, body mass index, cancer antigen 125 concentration, tumor size, tumor rupture, positive cytology, ovarian surface involvement, retrieved lymph nodes, use of laparoscopy, fertility-sparing and ovary-sparing procedures, complete staging and restaging, and adjuvant chemotherapy. However, the incidences of advanced stage (II-III) tumors (10.3% vs 36.4%, P=0.001), microinvasion (2.1% vs 15.2%, P=0.012), peritoneal implants (8.3% vs 33.4%, P<0.001), and lymph node involvement (0% vs 21.2%, P<0.001) were significantly higher in patients with micropapillary than with typical SBOT. Five patients with typical (5.2%) and three with micropapillary (9.1%) SBOT had recurrent disease (P=0.418), and one patient (3%) in micropapillary SBOT group died due to the disease (P=0.254). The 5-year disease-free survival (DFS) rates for patients with typical and micropapillary SBOT were 96% and 86%, respectively (P=0.148). All three patients with micropapillary SBOT who had recurrence had peritoneal implants (one noninvasive and two invasive). Multivariate analysis showed that peritoneal implant was the only significant factor related to DFS (P=0.002). CONCLUSIONS: Because micropapillary SBOT was significantly associated with peritoneal implants, especially invasive implants, and lymph node involvement, complete staging procedures, including lymph node dissection, are recommended. However, micropapillary SBOT itself was not significantly associated with DFS. Peritoneal implant was the only factor independently associated with tumor recurrence.

Positive experience of intraperitoneal chemotherapy followed by intravenous chemotherapy in heavily pretreated patients with suboptimal residual ovarian cancer and primary peritoneal cancer.

AIMS AND BACKGROUND: To assess feasibility and toxicity of intraperitoneal administration of cisplatin and paclitaxel, followed by intravenous chemotherapy in pretreated patients with suboptimal ovarian cancer (residuum >1 cm) or primary peritoneal tumor, and suffering from ascites and/or intestinal obstruction. METHODS: Fourteen relapsed ovarian cancer patients, 5 of whom were platinum sensitive (platinum-free interval >6 mo), 7 platinum-resistant (platinum-free interval <6 mo), and 2 platinum-refractory, received one cycle of intraperitoneal cisplatin, 100 mg/m2 on day 1, and two cycles of intraperitoneal paclitaxel, 120 mg/m2 on days 8 and 14. Intravenous chemotherapy was administrated 4 weeks following the last intraperitoneal paclitaxel instillation. Blood and peritoneal fluid samples were harvested at 0, 1, 4 and 24 h after ending paclitaxel delivery to guarantee proper tumor exposure and patient safety. RESULTS: Intraperitoneal cisplatin determined 6 cases of vomiting grade 1-2 (40% of the morbidity). Intraperitoneal paclitaxel was associated with 6 events of grade 1-2 abdominal pain; the only grade 4 toxicity was one case of neutropenia and one of mucositis. Ascites decreased in 11 patients: the median time to first need for paracentesis was 5 months, compared to a median baseline paracentesis of 4 weeks. Three intestinal normalizations were obtained. The median overall survival was 10 months for our cohort of patients. Intraperitoneal paclitaxel clearance was significantly higher in patients with suboptimal tumor and symptomatic disease than in patients with smaller residual masses and without ascites (P = 0.004). CONCLUSIONS: Intraperitoneal treatment was feasible, and enhanced response to the following intravenous chemotherapy was seen in these patients.

[Therapeutic effect of docetaxel combined with oxaliplatin for treatment of recurrent epithelial ovarian cancer].

OBJECTIVE: To evaluate the efficacy and safety of docetaxel (Taxotere) (DTX) and oxaliplatin (OXA) for treatment of recurrent epithelial ovarian cancer. METHODS: Thirty-six patients with histologically confirmed recurrent epithelial ovarian cancer received chemotherapy with DTX and OXA. DTX at the dose of 75 mg/m(2) was administered on day 1 by intravenous infusion in 60 min, followed by OXA at 100 mg/m(2) given by a 2 h infusion. The chemotherapy cycles were repeated every 21 days, and the patients received at least 2 cycles. RESULTS: All the patients were available for response evaluation, among whom 3 (8.3%) showed complete responses and 17 (47.2%) showed partial responses, with an overall response rate of 55.6%. The main adverse effects included hematological toxicities and peripheral neuropathy. CONCLUSION: Combination of DTX and OXA produces good therapeutic effect with tolerable toxicity profile for treatment of recurrent epithelial ovarian cancer.

Favorable effects of long-term therapy with gonadoliberin analogues in three patients with advanced and recurrent ovarian cancer.

BACKGROUND: Numerous scientific reports indicate a high possibility of gonadotrophin involvement in ovarian cancer neoplasia. CASE PRESENTATION: In a 49-year-old patient with recurrent ovarian cancer, a present survival of ten years has been achieved. She has been using GnRH analogues for nine years. A 32-year-old patient with a primary highly advanced ovarian cancer received standard therapy and additional implants with GnRH analogues as consolidation therapy for 20 months. Overall survival is 14 years. In a 56-year-old patient with advanced ovarian cancer GnRH analogues were used as consolidation therapy for seven years, achieving seven years of a complete clinical remission and nine and a half years of survival up to now. CONCLUSION: It seems that gonadoliberin analogues should find their place in ovarian cancer therapy.

[Association of EGFR expression with angiogenesis and chemoresistance in ovarian carcinoma].

OBJECTIVE: To clarify the association of EGFR expression with angiogenesis and chemoresistance in ovarian cancer. METHODS: Immunohistochemical PV-6000 staining was used to detect the expression of EGFR, LRP protein and MVD in 102 ovarian tumor specimens. RESULTS: EGFR, LRP positive rates and MVD in borderline and malignant ovarian specimens were significantly higher than those in the normal and benign ones (P < 0.01). EGFR positive expression rate in stage III-IV carcinoma tissues, poor differentiation and with ascites was higher than that in stage I-II carcinomas of well differentiation and without ascites (P < 0.05). MVD was related to histological grade, residual tumor and ascites, LRP positive expression had no correlation with the clinicopathologic parameters (P > 0.05). The effective rate of chemotherapy in patients with EGFR and LRP-positive expression were 57.1% and 53.7%, respectively, significantly lower than that in cases with EGFR and LRP-negative expression (85.0% and 90.9%, P < 0.05). In the 64 cases with complete data, the three-year survival rate was 53.0%. The survival time was shorter in the cases with EGFR and LRP-positive expression, poor differentiation, ascites and chemoresistance (P < 0.01), and only LRP-positive expression and chemotherapeutic effect were independently related to survival time (P < 0.05). There was a correlation between EGFR and MVD (r = 0.548, P < 0.01), EGFR and LRP positive expression (P = 0.020). CONCLUSION: The expression of EGFR in ovarian cancer is related to angiogenesis and chemoresistance. EGFR and LRP-positive expression are related to chemoresistance, and detection of the two proteins may be helpful in guiding chemotherapy choice for ovarian cancer. LRP-positive expression and chemotherapeutic effect may be independent prognostic factors.