Search

Background: Due to the increasing amount of published data suggesting that endometrial carcinoma is a heterogenic entity with possible different treatment sequences and post-treatment follow-up, the Polish Society of Gynecological Oncology (PSGO) has developed new guidelines. Aim: to summarize the current evidence for diagnosis, treatment, and follow-up of endometrial carcinoma and to provide evidence-based recommendations for clinical practice. Methods: The guidelines have been developed according to standards set by the guideline evaluation tool AGREE II (Appraisal of Guidelines for Research and Evaluation). The strength of scientific evidence has been defined in agreement with The Agency for Health Technology Assessment and Tariff System (AOTMiT) guidelines for scientific evidence classification. The grades of recommendation have been based on the strength of evidence and the level of consensus of the PSGO development group. Conclusion: Based on current evidence, both the implementation of the molecular classification of endometrial cancer patients at the beginning of the treatment sequence and the extension of the final postoperative pathological report of additional biomarkers are needed to optimize and improve treatment results as well as to pave the route for future clinical trials on targeted therapies.

// Jacek J. Sznurkowski 1 , Anton Żawrocki 2 , Katarzyna Sznurkowska 3 , Rafal Peksa 2 and Wojciech Biernat 2 1 Department of Oncological Surgery, The Medical University, Gdansk, Poland 2 Department of Pathology, The Medical University, Gdansk, Poland 3 Department of Pediatrics, Pediatric Gastroenterology, Hepathology and Nutrition, The Medical University, Gdansk, Poland Correspondence to: Jacek J. Sznurkowski, email: jacek.sznurkowski@gumed.edu.pl Keywords: vulvar SCC, PD-L1, HPV, p16, prognosis Received: July 13, 2017 Accepted: August 29, 2017 Published: September 15, 2017 ABSTRACT Background: Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies. Aim: To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it’s clinicopathological and prognostic significance. Methods: Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results: PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037). PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.

// Jacek J. Sznurkowski 1 , Anton Żawrocki 2 and Wojciech Biernat 2 1 Department of Oncological Surgery, The Medical University, Gdansk, Poland 2 Department of Pathology, The Medical University, Gdansk, Poland Correspondence to: Jacek J. Sznurkowski, email: jacek.sznurkowski@gumed.edu.pl Keywords: vulvar SCC, p16, TILs, TAMs, prognosis Received: December 29, 2016 Accepted: April 04, 2017 Published: May 03, 2017 ABSTRACT Background: The p16 Ink4a is not a surrogate marker for high-risk human papilloma virus (HPV) genotypes but indicates better prognosis in vulvar squamous cell carcinoma patients. Our recent study confirmed substantial mismatch between p16 Ink4a and high-risk HPV-status as well as revealed that p16 Ink4a -overexpression itself is an independent prognostic factor for vulvar cancer. Aim: To determine significance of the tumor infiltrating immune cells and p16 Ink4a –status for better outcome of patients with vulvar cancer. Methods: Intraepithelial tumor infiltrating lymphocytes: CD8+, CD4+, FOXP3+, CD56+, tumor associated macrophages: CD68+, and GZB+ cells were calculated in 85 vulvar squamous cell carcinomas with previously defined p16 Ink4a and high-risk HPV-status. Number of intraepithelial CD8+, CD4+, FOXP3+, CD56+, CD68+ and GZB+ cells were compared between tumors with different p16 INK4a status and overlapping high-risk HPV-status separately. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results: p16 Ink4a -negative tumors were more infiltrated by intraepithelial CD8+, CD4+ and GZB+ cells than p16 Ink4a -positive tumors (p=0.032, p=0.016 and p=0.007 respectively). High-risk HPV-status did not correlate with the infiltration of immune cells. Median follow up was 89.20 months (range 1.7-189.5). High CD4+ and CD56+ indices were correlated with prognosis in p16 Ink4a –positive cases (p=0.039 and p=0.013 respectively). Low CD68+ infiltrates were correlated with prognosis in p16 Ink4a -negative cases (p=0.018). Conclusion: p16 Ink4a -status impacts local immune surveillance as represented by tumor infiltrating immune cells. Immunologic effects contributing to clinical outcome might depend on p16 Ink4a -overexpression.

Introduction/Background Strategy of treatment in patients with recurrent ovarian cancer (OC) dependents on platinum-free interval (PFI). We aimed to compare survival in ‘platinum resistant’ OC patients who received platinum-based or non-platinum chemotherapy at first relapse in real world practice based. Methodology Data of OC patients treated with primary debulking surgery and standard chemotherapy (paclitaxel/platinum analogs) between January 1, 2011 and December 31, 2011 were extracted from Polish National Health Fund Database. Further overall survival (OS) was compared between patients who received any type of chemotherapy up to 6 months PFI. Results 17% (227/1369) patients classified as ‘platinum-resistant’ by the 6-month threshold of PFI and 29% (66/227) of those group, were treated with Pt-based chemotherapy at second line. Median OS after platinum-based 2-nd line chemotherapy was significantly longer compared to non- platinum chemotherapy group (median OS was 28.1 months, 95% CI: 23.3–42.0 vs. 16.4 months, 95% CI: 13.1–21.0; HR=0.71, 95% CI, 0.51–0.99; P=0.049). This effect was seen, among patients with PFI of 3–6 months (median OS was, 28.1 months, 95% CI: 23.1–42.0 vs 14.3 months, 95% CI: 10.4–40.5, respectively; HR=0.61, 95%CI, 0.39–0.96; P=0.0336). but not in PFI Conclusion Our results from real world data based on nationwide population cohort study shows that six-months PFI as an arbitrary threshold for subsequent Pt-based chemotherapy is questionable. Biomarkers of platinum sensitivity are needed to identify potential responders, especially in group of patients with PFI 3–6 months. Disclosure Nothing to disclose.

Epidermal growth factor-like domain-containing protein 7 (Egfl7) is a secretive gene-encoded protein expressed in endothelial cells of blood vessels, where it...

In December 2015, representatives of the European Society for Medical Oncology (ESMO), the European Society of Gynaecological Oncology (ESGO) and the...

Background/Aims: To determine the proportion of T-regulatory cells (CD4+CD25highFOXP3+ cells) in peripheral blood and the number of FOXP3+ cells in intestinal mucosa of children with inflammatory bowel disease (IBD), and to verify whether these parameters correlate with the activity of the disease.Material and methods: 24 patients newly diagnosed for IBD were included in the study: ulcerative colitis (UC; n = 13) and Crohn’s disease (CD; n = 11). Seventeen healthy controls (HC) and 16 patients with irritable bowel syndrome (IBS) served as a control group for peripheral and intestinal Tregs assessment, respectively. The disease activity was assessed by Pediatric Ulcerative Colitis Activity Index (PUCAI) and Pediatric Crohn’s Disease Activity Index (PCDAI). Quantification of regulatory T cells of CD4+CD25highFOXP3+ phenotype in peripheral blood was based on three-color flow cytometry. Mucosal Tregs represented by FOXP3+ cells were evaluated using immunohistochemistry.Results: Median proportion of CD...

Background We aimed to evaluate the correlation between p16ink4a-overexpression and high risk (hr)HPV-DNA in vulvar squamous cell carcinoma (vSCC) tumors as well as the impact of both biomarkers on the prognosis of vSCC patients. Methods PCR-detection of (hr)HPV-DNA and immunohistochemical staining for p16ink4a were conducted in 85 vSCC tumors. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results p16ink4a-overexpression and (hr)HPV-DNA were detected in 35 and 37 of the 85 tumors, respectively. Among the 35 p16ink4a-positive tumors, 10 lacked (hr)HPV-DNA (29 %). Among the 50 p16ink4a-negative tumors, (hr)HPV-DNA was detected in 12 cases (24 %). The median follow-up was 89.20 months (range 1.7–189.5 months). P16ink4a-overexpression, but not (hr)HPV-DNA positivity of the primary tumor, was correlated with prolonged overall survival (OS) (p = 0.009). P16ink4a-overexpression predicted a better response to radiotherapy (p

Background The resection of all visible malignancies increases the likelihood for long-term survival in epithelial ovarian cancer. The complete extinguishment of pelvic disease is possible using en bloc pelvic resection. The no-touch isolation technique aims to reduce cancer cells flowing from the primary tumor site to the liver and other organs by ligating blood and lymphatic vessels first. objectives are to present the operative details and to establish the feasibility of the modified technique of en bloc pelvic resection, which begins with the central ligation of vessels supplying the tumor bed. Methods Twenty patients with pelvic tumor extensively infiltrating into adjacent pelvic organs were uniformly operated on. The surgical plan commenced with incisions along the lateral peritoneal reflections immediately medial to the white line of Toldt followed by a retroperitoneal central ligation of ovarian and mesenteric vessels and the ovarian lymphovascular flow. Then, the routine steps of en bloc pelvic resection were performed. Data on treatment were assessed. Results In all cases, no gross residual disease was achieved. The median durations of the surgical procedure and the hospital stay were 320 min (range: 205–430 min) and 12 days (range: 7–44 days), respectively. The complications were as follows: wound infection (n = 1), anastomosis dehiscence (n = 1), total parenteral nutrition (n = 4), and death (n = 1, PE). The median follow-up time period was 19 months (range: 8–31 months). No patient experienced a recurrence of pelvic disease. Conclusions Performing a central ligation of vessels supplying the tumor bed prior to an en bloc pelvic resection is feasible with acceptable morbidity and mortality rates.

The prognostic impact of the number of affected lymph nodes and subsequent benefit of irradiation for patients with vulvar squamous cancer are still controversial. This brief commentary is related to a previously published paper in this journal, and suggests that most of the conflicting results on the prognostic impact of the irradiation of patients with single lymph node metastasis originate from the unclear role of human papillomavirus (HPV) infection in response to adjuvant radiotherapy in vulvar cancer patients. Now that we know certain HPV-related cancers are very sensitive to radiotherapy and have a better prognosis than those unrelated to HPV, future research may focus on appropriate cases for adjuvant treatment going forward.

Purpose We compared response, survival and side effects of regiments with intravenous cyclophosphamide followed by intraperitoneal cisplatin versus intravenous cyclophosphamide followed by intraperitoneal carboplatin as second line treatment in one center retrospective study. Material and Methods Inclusion criteria were: relapse or recurrence of the disease after surgery and first line treatment; stage III histologicaly documented serous epithelial ovarian cancer after one or more prior regiments of chemotherapy. Recurrence were confirmed throughout restaging laparotomy or second look laparotomy. Patients from one of the groups received 90mg/m2 cisplatin on the first day and 750mg/m 2 cyclophosphamide intravenously, while the second group members AUC 6 carboplatin intraperitoneally and 750mg/m 2 cyclophosphamide intravenously. Four courses were administrated for each patient. Results Of the 49 patients in the cisplatin group the response rates were 21 (43%), 10 (20%) and 18 (37%) in the groups of pathologic complete response, pathologic partial response and progressive disease, respectively. The median survival from the initiation of intraperitoneal chemotherapy was 59 months. Of the 25 patients in the carboplatin group the response rates were 10 (40%), 4 (16%) and 11 (44%) respectively. The median survival -51 months. The differences between the groups were not statistically significant p>0.05 either in response or in toxicity. Conclusions The results of our research including relatively long survival from intraperotoneal chemotherapy initiation confirm that carboplatin treatment is as good as cisplatin in second line intraperitoneal chemotherapy for ovarian cancer.

Objective Regulatory T cells (Tregs), and the enzyme indoleamine 2,3-dioxygenase (IDO), have potential regulatory properties for immune escape in cancer. Inhibitors of IDO are available and could potentially be used in vulvar cancer if IDO was proved to drive progression of the disease. The aim of this study was to evaluate the expression of factor forkhead boxP3 (FOXP3), a marker of Tregs, and IDO in vulvar squamous cell carcinoma (vSCC), and to verify their prognostic significance. Methods 76 primary tumors and 35 lymph node metastases derived from 76 patients with full clinical history were analyzed. The intratumoral infiltration of Tregs and IDO expression within cancer were evaluated by immunohistochemistry. Results The number of Tregs in primary tumor and in corresponding lymph node metastasis was significantly correlated. Intensity of Treg infiltrates in the primary and metastatic sites was not correlated to IDO expression and had no influence on the overall patient survival. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age. Conclusions The degree of intratumoral Treg infiltrates is an individual feature and remains stable throughout the course of the disease without impact on the patient's survival. IDO expression predicts shorter survival of vSCC patients. If immunologic tolerance of the tumor is promoted by the overexpression of IDO it will not influence the number of intratumoral Tregs. IDO expression seems to be an independent prognostic factor in patients with vSCC.

To investigate whether asymmetry exists in the left- and right-distribution of ovarian cystic lesions in women with endometriosis.We evaluated operative reports of women who underwent surgical treatment of endometrioma(n = 253) from January 1999 to December 2003. We included only those cases that had not been previously operated on (n = 234). Data of all operative findings consisted of a written report and a diagram, fulfilling the revised American Fertility Society Classification of endometriosis.Endometrioma was found in the left ovary in 113 women, in the right ovaryin 67, and bilaterally in 54. Left ovarian unilateral endometrioma was found more frequently (62.8%) than right endometrioma (p0.001, odds ratio (OR) 2.8, 95% confidence interval (CI) 1.9, 4.4). The frequencies of left and right ovarian endometrioma were compared with the expected 50% using Pearson's chi(2)-test. The results confirmed asymmetry(p = 0.001). We found 4 cases of ovarian cancer associated with left endometrioma without histological proof of transition.Our results confirm a left lateral predisposition of endometrioma. This predisposition may be caused by the presence of the sigmoid colon in the left side of the pelvis, which decreases peritoneal fluid movement. Our findings may support the transplantation theory of the origin for endometriosis.

Background: The p16INK4a is not a surrogate marker for high-risk human papilloma virus genotypes (hr)HPV-DNA) and was suggested to indicate better prognosis of vulvar squamous carcinoma (vSCC). Our recent study confirmed substantial mismatch between p16ink4a and (hr)HPV-status as well as prognostic significance exclusively for p16INK4a-overexpression in cohort of 85 patients. Aim: To compare the infiltration of tumor infiltrating lymphocytes (TILs) and to assess their prognostic significance in cases having tumors with opposed p16INK4a and (hr)HPV-status. Methods: TILs (CD8+, CD4+, FOXP3+, CD68+, CD56+ and GzB+ cells) were calculated in 85 vSCCs with previously defined p16INK4a and (hr)HPV-status. Number of intraepithelial (IE) TIL-subtypes were compared between tumors with different p16INK4a and (hr)HPV-status separately. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: p16INK4a-negative tumors were infiltrated more intensely by CD8+, CD4+ and GZB+ cells than p16INK4a-positive vSCCs (p = 0.032, p = 0.016 and p = 0.007 respectively). (hr)HPV-status did not impact the infiltration of TILs. Median follow up was 89.20 months (range 1.7-189.5). High (IE)CD4+ infiltrates were prognostic in general cohort and in p16INK4a-positive cases (p = 0.032 and p = 0.039 respectively). High (IE)CD56+ infiltrates were correlated with prognosis in p16INK4a-positive and (hr)HPV-positive cases (p = 0.013 and p = 0.0458 respectively) while high (IE)CD68+ infiltrates were inversely correlated with survival in cases with p16INK4a-negative and (hr)HPV-negative tumors (p = 0.018 and p = 0.0441 respectively). Conclusion: p16INK4a-status modulates local immune surveillance as represented by TILs. Immunologic effects contributing to clinical outcome might depend on p16INK4a-overexpression. Citation Format: Jacek J. Sznurkowski, Anton Zawrocki. p16INK4a status of primary tumor modulates local immune response in vulvar squamous cell carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A136.

Objective In 2009, FIGO modified staging of vulvar cancer — the performance of the new classification relative to the prior system has not been assessed. We sought to investigate the impact of the 2009 FIGO vulvar cancer staging system on stage distribution and prognostic ability of the 2009 sub-stage classifications in a large cohort of uniformly staged cases with long-term followup. Methods Patients undergoing surgery for vulvar cancer were identified from 2 institutions (Mayo Clinic and Medical University, Gdansk, Poland) using a similar surgical approach. Inclusion criteria required primary surgery for invasive vulvar cancer for cases with >1mm invasion with complete inguinal/femoral lymphadenectomy. The technique of inguinofemoral node dissection used in both institutions was designed to remove both superficial and deep inguinofemoral nodes. A retrospective review was performed and all cases were assigned stage using the 1988 and 2009 FIGO systems after reviewing pathology slides. Cause-specific survival (CSS, death due to cancer) was estimated using the Kaplan–Meier method and compared using the Cox proportional hazards model t for the first 10years after surgery. Result A total of 468 patients met inclusion criteria. Thirty-one percent (n=155) were down-staged, and 1 case up-staged using 2009 staging. The new system fails to effectively separate 10-yr CSS for stage I and II cases (p=0.52), while FIGO 1988 failed to separate stages II and III (p=0.41). We observed a difference in survival for stage I and II cases based on tumor diameter. For smaller stage II lesion (≤4cm vs. >4cm) we observed no difference in survival compared to all stage IB cases (p=0.25) Considering node positive disease, patients with 2009 FIGO stages ΙΙΙA, ΙΙΙB, and ΙΙΙC were not significantly different in terms of CSS (p=0.17). However, CSS approached significance between patients with extracapsular vs. intracapsular disease (p=0.072). For stages IIIA and IIIB (excluding extracapsular spread, IIIC), we observed that the number of positive nodes and diameter of lymph node metastasis were not significantly associated with CSS. When comparing bilateral nodal involvement vs. unilateral cases with at least 2 involved nodes, we found no statistical difference in CSS (p=0.30). Conclusion This is the largest cohort study to evaluate the effect and prognostic performance of the new FIGO vulvar cancer staging system. The new staging does not stratify survival between stages I and II and reduces CSS in stage I cases. Our results suggest that lesion size in node negative cases is an important prognostic variable that could be addressed in future staging classifications. Among the node positive cases, the current classification results in slight differences in CSS, primarily between intra- and extra-capsular disease and not according to the number of positive nodes and lymph node metastasis diameter. Finally we observe that bilateral nodal disease does not appear to impact CSS, justifying it being omitted from the 2009 staging system and that separating node positive (2009 stage III) from node negative (2009 stage II) cases is justified.

Background:The clinicopathological significance of the local spontaneous immune reaction in vulvar squamous cell carcinoma remains unclear. The purpose of this study was to clarify the role of the subtypes of tumor-infiltrating lymphocytes, both individually and synergistically.Methods:Seventy-six patients with verified histopathological data and complete clinical history were included into the study. We collected 76 paraffin-embedded samples of the primary tumor. The presence of CD4+and CD8+T cells was evaluated by immunohistochemistry and compared with commonly recognized prognostic factors. The primary end point analyzed was the overall survival.Results:CD4+and CD8+T cells were detected both within the nests of carcinoma and in the stroma, but only the infiltration within cancer cell nests was further analyzed. There was significant positive correlation (Spearman rho testR= 0.282,P= 0.014) between the number of intratumoral CD4+and CD8+T cells. No correlation was observed between the number of tumor-infiltrating CD4+and CD8+T cells and the patients' survival. Patients were classified into the following 4 groups (CD4+/CD8+, CD4−/CD8−, CD4+/CD8−, CD4−/CD8+), but none of them correlated with overall survival.Conclusions:These data support the statement that CD4+and CD8+T cells cooperate within cancer cell nests, but this spontaneous immune reaction is an individual feature not influencing the prognosis. Intratumoral CD4+T cells might control or reflect the immune responses against cancer cells, whereas CD8+T cells do not seem to work as sufficient effectors in tumor tissues.

The objective of this study was to find prognostic factors for the development of recurrences in patients who had undergone surgical treatment of vulvar cancer.The records of patients with primary vulvar cancer (n=104) treated at the Department of Gynaecological Oncology of the Medical University of Gdańsk between 1998 and 2001 were reviewed to identify those with squamous histology. Of the 93 thus identified 27 were excluded because of lack of standard treatment and 7 because of lack of radical surgery. A total number of 59 patients with squamous cell carcinoma were finally analyzed. For each record the age of the patient, size of the lesion, depth of invasion, margins of resection and lymph node status were analyzed. All patients were staged according to FIGO (1996). Recurrences were recorded by localization, whether local, groin or distant, and compared with a group of patients without any recurrences after radical surgery (n=59).Recurrence was recorded in 19 cases (28.8%). A local (vulvar/perineal) recurrence was diagnosed in 10 patients (10/59, 16.9%), while 5 (5/59, 8.5%) developed groin recurrence and 4 (4/59, 6.8%) had distant recurrences. Multifocality of the primary tumour is an independent risk factor for local recurrence (HR: 3.12; 95% CI: 0.84-11.6). A metastatic node was the only independent prognostic risk factor for groin or distant recurrence (HR: 3.16; 95% CI: 0.94-10.2).Close follow-up of patients treated for vulvar cancer is recommended to detect recurrences at an early and potentially curable stage. Deep inguinal-femoral lymphadenectomy could be replaced with superficial inguinal groin dissection.

To compare clinical characteristics of infertile and fertile patients with endometriosis.We evaluated medical records of women who underwent surgical treatment of endometriosis (n=284) between January 1999 and December 2003. Our study included only cases of histopathologically proven pelvic endometriosis (n=269). These patients were categorized into two groups named after infertile (n=45) and fertile cases (n=224). Clinical data were compared.Infertile patients are younger (t student. P=0.0000), have lower weight (Wilcoxon test P=0.0150), lower blood pressure--either systolic (Wilcoxon test P=0.0006) or diastolic (Wilcoxon test P=0.0007), separate noncystic endometriotic leasions occur frequently among these cases (Pearson chi-square P=0.000).Noncystic endometriotic implants are more strongly related to infertility than endometriomas. The relationship between blood pressure and infertility requires further investigation. endometriosis.

Epidermal growth factor like domain 7 (Egfl7) is expressed by endothelial cells in normal tissues and by malignant cells in various human tumors. Aim: to analyze patterns of immunohistochemical (IHC) staining of Egfl7 within high grade serous ovarian cancer (HGSOC) tissue and to assess clinical value of this biomarker. Material and methods: The IHC staining and pathological analyses were performed on paraffin-embedded primary tumours collected from 73 HGSOC patients with verified clinical history. Mouse anti-human monoclonal antibody against Egfl7, was used. Egfl7 expressing tumors were classified qualitatively in accordance to intense of staining (HSCORE). The appropriate statistical analyses were performed. P-values of Results: Egfl7 was expressed by the cancer cells within 63 of 73 primary HGSOC tumors (68.3%). Endothelial expression of this biomarker was sporadic. Cancer cells presented two patterns of staining: cytoplasmic only in 50/72 cases (69.4%) and nuclear/cytoplasmic in 13/72 cases (18%). Median duration of the follow-up was 47.25 months (range 17–79 months) Cytoplasmic expression of Egfl7 was not correlated with any of clinico-pathological features as well as with prognosis. The presence of nuclear/cytoplasmic staining within HGSOC predicts worse response for chemotherapy and correlates with increased preoperative levels of CA125. Conclusion: Cancer endogenous expression of Egfl7 is frequent within HGSOC tissue. Predictive value of nuclear/cytoplasmic staining of Egfl7 for chemoresistance should be further evaluated. Citation Format: Jacek Jan Sznurkowski, Anton Zawrocki, Maciej Pawlowski. Clinical value of immunohistochemical expression of EGFL7 within high-grade serous ovarian cancer tissue. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A44.

Objective In 2009, International Federation of Gynecology and Obstetrics (FIGO) modified staging of vulvar cancer—the prognostic significance of the new classification relative to the prior system as well as to the commonly recognized prognostic factors has not been assessed. The aim of this study was to test prognostic ability of 2009 staging in a cohort of uniformly treated and staged cases with long-term follow-up. Methods Pathologic characteristics were obtained by blind review of the original tissue samples. 76 patients who qualified for surgery on the basis of the same criteria, with full clinical history, were included in the study. The histological analyses were performed on 76 and 35 paraffin-embedded tissue samples from primary tumors and lymph nodes, respectively. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results Univariate analysis has demonstrated that age (p = 0.0170), lymph node metastasis (p = 0.0393), tumor grade (p = 0.0086) and FIGO1994 stage (p = 0.001) were the significant prognostic factors for overall survival. Multivariate analysis has demonstrated that growing age (HR 2.25, 95 % CI 0.79–3.71, p = 0.0321), tumor grade (G1 vs. G2 and G3) (HR 1–3.11, 95 % CI 1.6–4.62, p = 0.0057) and FIGO1994 stage (HR 1.78, 95 % CI 0.55–3.01, p = 0.0061) are independent prognostic factors with respect to overall survival. Conclusions The results indicate the prognostic advantage of the 1994 FIGO staging as it has become an independent prognostic factor in contrast to the new FIGO system. This should be tested in future larger cohort studies. Differentiation grade turned out to be a very valuable independent prognostic factor and should be incorporated as a routine component of the histopathologic reports in vulvar cancer.

Objective Adaptive immune effectors do not influence prognosis in vulvar squamous cell carcinoma (vSCC). Therefore, we tried to clarify the prognostic role of innate immunity and granzyme B-dependent cytotoxicity as defined by intratumoral infiltrates of natural killer cells (CD56+) and lymphocytes expressing granzyme B (GrB+). Methods We analyzed 76 primary vSCCs and 35 lymph node metastases that were obtained from 76 patients with a full clinical history. The distribution and density of GrB+ and CD56+ cells within cancer tissues were evaluated by immunohistochemistry and correlated with clinicopathological features, commonly recognized prognostic factors and overall survival (OS). Results CD56+ cells were mostly detected within the cancer nests, while GrB+ cells were predominant in the tumor stroma. Intraepithelial (IE) CD56+ infiltrates at the primary site were correlated with depth of invasion (r = 0.339, p = 0.003) and recurrence (r = 0.295, p = 0.011), while IE GrB+ infiltrates were correlated with tumor grade (r = 0.304, p = 0.009) and age (r = 0.333, p = 0.004). The primary cancer nests of metastatic patients were infiltrated more by intraepithelial (IE) CD56+ cells than were those of the non-metastatic patients (p = 0.05). The median OS was 41.16 months (range 1.7–98.43). High IE GrB+ infiltrates predicted longer OS among patients without metastases (p = 0.028). High IE CD56+ infiltrates were correlated with longer OS in metastatic cases (p = 0.009). Conclusion The combined cytotoxicity of innate and adaptive immune effectors infiltrating cancer nests (IE GrB+) predicts an improved clinical outcome among non-metastatic vSCC patients. The functional status of prognostic IE CD56+ infiltrates in immune escaped (metastatic) tumors requires further investigation.