Tumor Nuclear Grade Research Articles

KI-67 LI Expression in Triple-Negative Breast Cancer Patients and Its Significance.

Purpose:Triple-negative breast cancer (TNBC) is a subset of breast cancer which is known to carry a poor prognosis because of lack of targets for hormonal therapy. Research efforts have focused in recent years on discovering biomarkers of management in TNBCs. KI-67 Labelling Index (LI) is a nuclear protein which has proven to play diagnostic and prognostic roles in many cancers.Materials and methods:We analysed the expression of KI-67 LI by immunohistochemistry in TNBC cases from the University hospital. This expression was cross-checked against clinical-pathological criteria of TNBC patients and against Vimentin expression in TNBC patients with significant KI-67 expression.Results:KI-67 LI was significantly expressed in the majority of TNBC cases. This expression was significantly correlated with lymph node metastases, tumour invasion, high tumour nuclear grade, clinical stage, adverse survival outcome, and failure to achieve pathological complete response. TNBCs’ KI-67 LI expression was also correlated with Vimentin expression, the mesenchymal chief marker of the EMT phenomenon.Conclusion:Collectively, our study presents a strong argument for the use of KI-67 LI as a biomarker of aggressive, metastatic TNBC disease with poor outcome. This study, along with mounting evidence in the scientific literature, presents a case for the use of this nuclear protein in diagnosis, prognosis, and follow-up of patients with this difficult diagnosis.

Upregulation of HIF1-α via an NF-κB/COX2 pathway confers proliferative dominance of HER2-negative ductal carcinoma in situ cells in response to inflammatory stimuli

There are data to suggest that some ductal carcinoma in situ (DCIS) may evolve through an evolutionary bottleneck, where minor clones susceptible to the imposed selective pressure drive disease progression. Here, we tested the hypothesis that an impact of the inflammatory environment on DCIS evolution is HER2-dependent, conferring proliferative dominance of HER2-negative cells. In tissue samples, density of tumour-infiltrating immune cells (TIICs) was associated only with high tumour nuclear grade, but in 9% of predominantly HER2-negative cases, the presence of tumoral foci (‘hot-spots’) of basal-like cells with HIF1-α activity adjacent to the areas of dense stromal infiltration was noted. Results of in vitro analyses further demonstrated that IL-1β and TNF-α as well as macrophage-conditioned medium triggered phosphorylation of NF-κB and subsequent upregulation of COX2 and HIF1-α, exclusively in HER2-negative cells. Treatment with both IL-1β and TNF-α resulted in growth stimulation and inhibition of HER2-negative and HER2-positive cells, respectively. Moreover, ectopic overexpression of HIF1-α rescued HER2-positive cells from the negative effect of IL-1β and TNF-α on cell growth. Our data provide novel insight into the molecular basis of HER2-dependent proliferation of DCIS cells and indicate the NF-κB/COX2 → HIF1-α signalling axis as a dominant mechanism of DCIS evolution induced by inflammatory microenvironment. Presented findings also highlight the clinical significance of heterogeneity of DCIS tumours and suggest that HIF1-α might be considered as a predictive marker of disease progression.

Abstract P3-08-62: An evaluation of p53 overexpression as a predictor of prognosis and chemotherapy benefit in relation to subtypes in primary invasive breast cancer

Abstract Background: The p53 tumor suppressor gene is important for cell cycle regulation and DNA repair. Somatic p53 gene mutations are associated with poor prognosis. Mutations in the p53 gene result in prolonged stability of the protein that can be detected by immunohistochemical (IHC) techniques. The impact of p53 protein status was investigated using the disease-free survival (DFS) rates and the efficacy of adjuvant chemotherapy (anthracycline+/-taxane) in relation to breast cancer subtypes. Methods: Primary invasive breast cancer patients who underwent treatment from January 2002 to December 2018 were enrolled in this retrospective study. A total of 4463 primary breast cancer cases were analyzed. The factors investigated included nodal status, tumor size, nuclear grade, ER/PgR and HER2 status, p53 overexpression (cutoff point: 50%), and the Ki-67 index value (cutoff point: 20%). Breast cancer subtypes were categorized based on the IHC data derived from ER/PgR, HER2 and Ki-67 values in invasive tumors. DFS was calculated using the Kaplan-Meier method and evaluated using the log-rank test. Cox's proportional hazard model was used to perform univariate and multivariate analyses of the factors related to DFS. Median follow-up period was 85 months. Results: 1. p53 overexpression rate was 18.1% (n=808) in all of the cases. The p53 overexpression significantly correlated with ER/PgR negativity, HER2 positivity, higher Ki-67 index values and nuclear grade, positive nodes and larger tumors. Patients with p53 overexpression received chemotherapy more often than those without overexpression in adjuvant settings. HER2 type and triple negative (TN) type had significantly higher rates of p53 overexpression, but luminal A and B types had lower p53 overexpression rates. 2. Patients with p53 overexpression had significantly worse DFS in luminal A and B types. However, p53 overexpression was not predictive for DFS in HER2 enriched, luminal HER2 and TN types. Multivariate analysis revealed that p53 was a significant factor for DFS in luminal A/B types. 3. The efficacy of chemotherapy for DFS was investigated according to the subtypes and p53 status. Chemotherapy did not affect the DFS in relation to p53 status in luminal A/B and HER2 types. However, in the TN type, patients with p53 overexpression had marginally worse DFS in cases without chemotherapy. On the other hand, there was no difference in DFS in the cases with chemotherapy. These findings suggest that chemotherapy is effective in improving the DFS in TN cases with p53 overexpression. Conclusion: p53 overexpression correlated with a higher grade of malignancy and unfavorable prognosis in patients with Luminal A/B subtypes. Although p53 status did not correlate with the prognosis in HER2 and TN subtypes, patients with p53 overexpression may benefit from chemotherapy in cases with TN subtype in adjuvant setting. Citation Format: Reiki Nishimura, Tomofumi Osako, Yasuhiro Okumura, Masahiro Nakano, Mamiko Fujisue, Nobuyuki Arima. An evaluation of p53 overexpression as a predictor of prognosis and chemotherapy benefit in relation to subtypes in primary invasive breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-62.

Development of a Risk-stratified Approach for Follow-up Imaging After Percutaneous Thermal Ablation of Sporadic Stage One Renal Cell Carcinoma

ObjectiveTo analyze risk factors and patterns of RCC recurrence following percutaneous ablation for stage 1 tumors and develop risk-stratified follow-up imaging protocols. MethodBiopsy-proven sporadic stage 1 RCC patients treated with percutaneous microwave ablation (MWA) or cryoablation (CA) from 2002 to 2017 were included. Kaplan-Meier analysis was used to estimate local and distant recurrence-free survival, cancer-specific survival and metastatic-free survival. Multivariable models were used to identify risk factors associated with recurrence. ResultsA total of 256 patients with stage 1 RCC (215 T1a, 41 T1b) were treated with percutaneous MWA (178 subjects) or CA (78 subjects). Recurrence was identified in 23 patients (16 local, 7 distant). Clinical T stage (HR 2.46, 95% CI 1.06-5.72, P = .04) and tumor grade (HR 4.17, 95% CI 1.17-14.76, P = .03) were independent predictors of recurrence. Recurrence was not associated with Nephrometry score, cystic tumors, ablation modality (CA vs MWA) or gender. Five-year cancer-specific survival, and metastatic-free survival were 98.6% and 97.4%, respectively. Patients were stratified into 2 groups: reduced risk stage 1 (no risk factors) or elevated risk stage 1 (≥1 risk factor). Recurrence risk was higher in the elevated-risk group (HR = 3.19, 95% CI 1.35-7.53, P = .008). Five-year overall recurrence-free survival (local + distant) was higher in reduced-risk vs elevated-risk cohorts, 88% vs 69%, P = .005. ConclusionHigh nuclear grade or T1b tumors have increased recurrence risk following percutaneous thermal ablation for stage 1 RCC. Current postablation follow-up protocols may be modified for individual recurrence risk to allow more frequent imaging for elevated-risk patients, while enabling less frequent imaging for reduced-risk patients.

Surgical management of ductal carcinoma in situ of the breast: A large retrospective study from a single institution.

Management of breast ductal carcinoma in situ (DCIS) has various approaches with distinct institutional specific practice. Here, we review DCIS management in a single institution with emphasize on re-operation rates and outcome. Breast ductal carcinoma in situ cases diagnosed at the Nottingham Breast Institute between 1987 and 2017 were identified (n=1249). Clinicopathological data were collected. Cases were histologically reviewed, and different factors associated with primary operation selection, re-excision, presence of residual tumor in the re-excision specimens, use of radiotherapy and ipsilateral recurrences were analyzed. 34% of DCIS patients were initially treated by mastectomy and were more frequently symptomatic, of high nuclear tumor grade, size >40mm, and associated with comedo necrosis and Paget's disease of the nipple. Further surgery was due to involved or narrow surgical margins. Residual tumor tissue was detected in 53% of the re-excision specimens. Re-excision rates of patients treated with breast-conserving surgery (BCS) were reduced from approximately 70% to 23%, and the final mastectomy rates decreased from 60% to 20%. Changes in surgical practice with acceptance of smaller excision margins and more frequent use of local radiotherapy have led to a significant decrease not only in the re-excision rate but also in the final mastectomy rate together with non-significant reduction in 5- and 10-year local recurrence rates. Although BCS is increasingly the preferred primary surgical option for DCIS management, a proportion of low-risk DCIS patients continue to undergo re-excision surgery or completion mastectomy. Despite acceptance of smaller margins, recurrence rate is decreasing.

Abstract P2-08-56: Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer

Abstract Background It is still controversial to consider age as a prognostic factor into the treatment strategy of patients with T1N0M0 breast cancer. Aim The main purpose of this study was to evaluate the effect of age on recurrence risk in patients diagnosed with T1N0M0 breast cancer as well as compare the prognosis of young aged patients(YA,≤40 years old) to non-young aged patients(non-YA,>40 years old) by using a propensity score matching(PSM) analysis. Methods 365 patients with T1N0M0 breast cancer diagnosed between 2003 and 2016 who received surgery in Sun Yat-sen Memorial Hospital Breast Cancer Center were included.The recurrence free survival (RFS) and risk factors for recurrence were identified by using Kaplan-Meier method and Cox proportional hazards models. PSM was then used to reduce the confounding effect of known risk factors on prognosis and then to compare 5-year RFS rates in patients between two age groups. Results After a median follow up of 79 months, 54 patients developed recurrences and 5-year RFS was 87.6%. YA patients had lower RFS estimates (80.6%), compared to patients diagnosed in a later age (89.1% if older than 40-years old; P = 0.049). YA patients tended to have Her-2 positive, TNBC tumors, higher rate of Ki-67 expression and nuclear grade tumor. At multivariate analysis, Her-2 positive (HR 2.115; 95% CI 1.103-4.055, p=0.024) and TNBC (HR 2.963; 95% CI 1.485-5.914, p=0.002) resulted independent prognostic factors of patient with T1N0M0 breast cancer. In the subgroup analysis, we found significant poor RFS for YA patients with Her-2 positive breast cancer compared to the older counterparts(p=0.006) and YA patients were associated with significantly higher rates of the locoregional recurrence rather than metastasis(p=0.004), especially in first 5 years after diagnosis. After PSM, the baseline level and treatment status including tumor size, grade, HR status, Her-2 status, Ki67 expression breast surgery type and systemic adjuvant treatment(AST) of patients in the two age groups tended to be equal. As result, we found significant difference in the 5-year RFS between two age groups(p=0.008). Conclusion Based on equal treatment condition, young age at presentation conferred a worse prognosis in patients with T1N0M0 breast cancer is independent on other pathological features. Citation Format: Zhong W, Tan L, You N, Wang Y, Liang G, Liu Z, Ling Y, Tian Z, Gong C. Effects of young age on prognosis in patients with node-negative tumors 2 cm or smaller breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-56.

N-Acetylglucosaminyltransferase III (GnT-III) but not N-Acetylgalactosaminyltransferase-6 and 8 are Differentially Expressed in Invasive and In Situ Ductal Carcinoma of the Breast.

Mammary carcinoma is the most common malignant tumor in women, and it is the leading cause of mortality. In tumor context, glycosylation promotes post translational modifications necessary for cell progression, emerging as a relevant tumor hallmarker. This study aimed to analyze the association between polypeptide N-acetylgalactosaminyltransferase-6 (ppGalNAc-T6), -T8, N-acetylglucosaminyltransferase III (GnT-III) expression, Phaseolus vulgaris-leucoagglutinin (PHA-L), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) staining with clinic-histopathological factors from patients with pure ductal carcinoma in situ (DCIS) and DCIS with invasive ductal carcinoma (DCIS-IDC) of breast. Formalin-fixed and paraffin-embedded samples (n = 109) were analyzed. In pure DCIS samples GnT-III was over-expressed in comedo lesions (p = 0.007). In DCIS-IDC, GnT-III expression was associated with high nuclear grade tumors (p = 0.039) while the presence of PHA-L and WGA were inversely related to HER-2 expression (p = 0.001; p = 0.036, respectively). These findings pointed to possible involvement of GnT-III, ppGalNAc-T8, L-PHA and WGA as probes in prognostic evaluation of DCIS.

PIK3CA Mutational Status Is Associated with High Glycolytic Activity in ER+/HER2\u2212 Early Invasive Breast Cancer: a Molecular Imaging Study Using [18F]FDG PET/CT

PurposeIn PIK3CA mutant breast cancer, downstream hyperactivation of the PI3K/AKT/mTOR pathway may be associated with increased glycolysis of cancer cells. The purpose of this study was to investigate the functional association of PIK3CA mutational status and tumor glycolysis in invasive ER+/HER2− early breast cancer.ProceduresThis institutional review board-approved retrospective study included a dataset of 67 ER+/HER2− early breast cancer patients. All patients underwent 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography ([18F]FDG PET/CT) and clinico-pathologic assessments as part of a prospective study. For this retrospective analysis, pyrosequencing was used to detect PIK3CA mutations of exons 4, 7, 9, and 20. Tumor glucose metabolism was assessed semi-quantitatively with [18F]FDG PET/CT using maximum standardized uptake values (SUVmax). SUVmax values were corrected for the partial volume effect, and metabolic tumor volume was calculated using the volume of interest automated lesion growing function 2D tumor size, i.e., maximum tumor diameter was assessed on concurrent pre-treatment contrast-enhanced magnetic resonance imaging.ResultsPIK3CA mutations were present in 45 % of all tumors. Mutations were associated with a small tumor diameter (p < 0.01) and with low nuclear grade (p = 0.04). Glycolytic activity was positively associated with nuclear grade (p = 0.01), proliferation (p = 0.002), regional lymph node metastasis (p = 0.015), and metabolic tumor volume (p = 0.001) but not with tumor size/T-stage. In invasive ductal carcinomas, median SUVmax was increased in PIK3CA-mutated compared to wild-type tumors; however, this increase did not reach statistical significance (p = 0.05). Multivariate analysis of invasive ductal carcinomas revealed [18F]FDG uptake to be independently associated with PIK3CA status (p = 0.002) and nuclear tumor grade (p = 0.046). Size, volume, and regional nodal status had no influence on glycolytic activity. PIK3CA mutational status did not influence glycolytic metabolism in lobular carcinomas. Glycolytic activity and PIK3CA mutational status had no significant influence on recurrence-free survival or disease-specific survival.ConclusionsIn ER+/HER2− invasive ductal carcinomas of the breast, glucose uptake is independently associated with PIK3CA mutations. Initial data suggest that [18F]FDG uptake reflects complex genomic alterations and may have the potential to be used as candidate biomarker for monitoring therapeutic response and resistance mechanisms in emerging therapies that target the PI3K/AKT/mTOR pathway.

Fecal galectin-1 as a potential marker for colorectal cancer and disease severity

Background/Aim. Colorectal cancer (CRC) represents one of the most common cancers worldwide. CRC is frequently diagnosed at advanced stages with poor prognosis, indicating the need for new diagnostic and prognostic markers. The aim of this study was to determine systemic and fecal values of galectin- 1 (gal-1) and ratios between gal-1 and proinflammatory cytokines: tumor necrosis factor-alpha (TNF-?), interleukin-1 beta (IL-1?) and interferon gamma (IFN-?), in the patients with CRC and the relationship with clinicopathological aspects of the disease. Methods. The blood samples and feces liquid fraction of 58 patients with CRC were analyzed. The serum and fecal levels of TNF-?, IL-1? and IFN-? and gal-1 were measured using sensitive enzyme-linked immunosorbent assay (ELISA) kits. Results. The fecal level of gal-1 was increased in the CRC patients with higher nuclear grade and poor tumor tissue differentiation. The gal-1/TNF-? ratio in the serum and feces had a higher trend in the patients with the advanced tumor-nodemetastasis (TNM) stage as well as the detectable lymphatic and blood vessel invasion. The gal-1/TNF-? and gal-1/IFN-? ratios were increased in the serum of patients with presence of lung/liver metastasis or peritoneal carcinomatosis, while the enhanced gal-1/IL-1 ratio was detected only in the serum of patients with lung metastasis. A positive correlation between the gal-1 value in feces and histological differentiation of tumor and biomarkers alpha-fetoprotein (AFP) and cancer antigen- 19-9 (CA 19-9), respectively, was also observed. The fecal values of gal-1 higher than 13,708.29 pg/g presented a highly sensitive and specific marker for histological differentiation of tumor tissue. Conclusion. We believe that the predomination of gal-1 over pro-inflammatory cytokines TNF-?, IL-1? and IFN- ? in the patients with advanced and progressive CRC may implicate on an immunomodulatory role of gal-1 in the limiting ongoing proinflammatory processes. The fecal values of gal-1 can be used as a valuable marker for the severity of CRC.

IKBKB expression in clear cell renal cell carcinoma is associated with tumor grade and patient outcomes.

Inhibitor of nuclear factor kappa B kinase subunitB (IKBKB or IKKβ) is a key activator of the nuclear factorκB transcription factor pathway. Increased expression and/or aberrant activity of IKBKB have been observed in various types of human cancer. Three independent techniques, reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemistry, were used to demonstrate that IKBKB expression is decreased in clear cell renal cell carcinoma (ccRCC). Notably, the patients with upregulated IKBKB protein expression were characterized by higher nuclear grade tumors and significantly shorter survival. The findings indicate that IKBKB protein may be of clinical relevance in ccRCC, serving as a marker of poor prognosis and as potential target for adjuvant chemotherapies. Further studies are required to validate the prognostic and predictive value of IKBKB.

Pathological features and prognostic value of renal tumor thrombus

Objective To investigate the pathological features and prognostic value of renal tumor venous thrombus. Methods The clinical data of 55 cases of renal cell carcinoma with inferior vena cava tumor thrombus treated from January 2015 to January 2017 were collected and analyzed retrospectively, including 46 males and 9 females, with the mean age of 60 years (29-82 years), and the body mass index of 16.4-33.0 kg/m2 (mean 24.2 kg/m2). Renal tumors are located on the right side of 37 cases and on the left side of 18 cases. The diameter of the tumor was 2.0-21.1 cm (mean 8.0 cm). Mayo classification were 13 cases of grade 0, 11 cases of grade Ⅰ, 19 cases of grade Ⅱ, 7 cases of grade Ⅲ, and 5 cases of grade Ⅳ. The patients′ paraffin pathology was reviewed and the classification, grade, nuclear grade, tumor composition, and vascular wall adhesion were recorded. All patients were followed up after surgery and the relationship between the characteristics and the prognosis was analyzed. Results There were 47 cases of renal clear cell carcinoma and 8 cases of papillary renal cell carcinoma type 2. Nuclear grade was 4 cases of grade 1, 20 cases of grade 2, 25 cases of grade 3, and 6 cases of grade 4. There were 11 cases of large tumor necrosis, 6 cases of sarcoma, and 38 cases of focal or no necrosis. There were 20 cases of extensive blood vessels adhesion of cancer thrombus, and 35 cases of focal or no adhesion. Vascular adhesion was associated with pathological types and tumor types (P=0.021, P=0.036). The median follow-up duration was 17 months. The postoperative one-year survival rate was 87.3%. Overall survival was different in patients with different tumor types, vascular adhesion and nuclear grade, among which the overall survival rate (33.3%) of the sarcoma group was significantly lower than that of the non-necrotic group (84.8%, P=0.003) and large necrotic group (100.0%, P=0.002). Overall survival rate (65.0%) was significantly lower in the vascular extensive adhesion group than in the focal or non-adhesion group (94.3%, P=0.005). The survival rate decreased as nuclear grade increased, among which the overall survival rate of patients at level 1, 2, 3 and 4 were 100%, 95%, 80% and 50% respectively (P=0.045). There was no difference in survival among patients with different Mayo grading and pathological classification (P=0.426, P=0.604). Conclusions The pathology of tumor thrombus in renal cancer helps to predict prognosis. There is no significant difference in survival among patients with different pathological types and Mayo grades. Sarcoma, advanced tumor nuclear grade and vascular adhesion of tumor thrombus are adverse prognostic factors. Key words: Kidney neoplasms; Tumor thrombus; Pathological features; Prognosis

Possible predictive role of cancer/testis antigens in breast ductal carcinoma in situ.

Cancer/testis antigens (CTAs) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues, with the exception of the testes and placenta. Numerous immunohistochemical studies have reported associations between CTA expression and a negative estrogen receptor (ER) status in breast tumors, and demonstrated that CTAs are frequently expressed in tumors with higher nuclear grade. The expression of CTAs has not been studied as extensively in ductal carcinoma in situ (DCIS) as it has been in invasive breast cancer. The present retrospective study included archived paraffin-embedded specimens from 83 patients diagnosed with DCIS in the period between January 2007 and December 2014. The follow-up time for local recurrence ranged between 1 and 8 years (mean, 5.02 years). Antigens from the melanoma-associated antigen gene (MAGE) family, namely multi-MAGE-A, MAGE-A1, MAGE-A10 and New York esophageal squamous cell carcinoma 1 (NY-ESO-1) antigen, were evaluated by immunostaining and their subcellular location was investigated. Presence of tumor-infiltrating lymphocytes (TILs) was evaluated on all sections, together with the histopathological variables of DCIS. Specific tested antigens exhibited associations with histopathological parameters for DCIS and all demonstrated statistically significant associations with nuclear staining, simultaneous cytoplasmic and nuclear staining, and local recurrence. Antigen MAGE-A10 demonstrated a significant association with higher expression of ER (P=0.005) and higher tumor nuclear grade (P=0.001), cytoplasmic staining (P=0.029) and antigen NY-ESO-1 with higher tumor size (P=0.001), expression of TILs (P=0.001) and R1 resection (P=0.001). A χ2 test revealed significant associations between simultaneous cytoplasmic and nuclear staining and local recurrence (P=0.005), central necrosis (P=0.016), and the expression of ER (P=0.003) and progesterone receptor (PR) (P=0.010). Additional analysis revealed an association between antigen MAGE-A10 and TILs (P=0.05). Additional analysis of TILs indicated that they were significantly associated with tumor grade (P=0.023), central necrosis (P<0.001), ER (P=0.003) and PR (P=0.029). Overall, CTAs from the MAGE family (MAGE-A1, multi-MAGE-A and MAGE-A10) and NY-ESO-1 associate with histopathological predictive variables of DCIS. The expression of antigens NY-ESO-1 and MAGE-A10 could serve an important role in the treatment of patients with negative histopathological predictive variables, but further analysis is required. Simultaneous cytoplasmic and nuclear protein expression of MAGE-A family and NY-ESO-1 CTAs may represent an independent marker for local recurrence. Taken together, the present data suggest that CTAs are not perfect indicators of invasiveness for DCIS, but could inform treatment strategies for patients when taken in combination with other histopathological predictive variables. However, this was a small study and further larger studies will be necessary to confirm the current findings.

Association Between BRCA Status and Triple-Negative Breast Cancer: A Meta-Analysis.

Triple-negative breast cancer (TNBC) is a subtype of aggressive breast cancer and characterized by a lack of the expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2. BRCA genes are tumor-suppressor genes that are involved in DNA damage repair and mutations of BRCA genes may increase the risk of developing breast cancer and/or ovarian cancer due to defective DNA repair mechanisms. However, the relationship between BRCA status and TNBC needs to be further investigated and validated. The aim of this meta-analysis was to evaluate the association between BRCA status and TNBC. We systematically searched the electronic databases of MEDLINE (PubMed), Embase, and Cochrane Library to identify relevant publications from April, 1959 to November, 2017. The data from the studies were examined by a meta-analysis using STATA software to calculate the odds ratio (OR) with 95% confidence interval (CI) by fixed-effect and random-effect models. We identified 16 qualified studies from 527 publications with 46,870 breast cancer patients including 868 BRCA1 mutations (BRCA1Mut) carriers, 739 BRCA2 mutations (BRCA2Mut) carriers, and 45,263 non-carriers. The results showed that breast cancer patients with BRCA1Mut carriers were more likely to have TNBC than those of BRCA2Mut carriers (OR: 3.292; 95% CI: 2.773–3.909) or non-carriers (OR: 8.889; 95% CI: 6.925–11.410). Furthermore, high expression of nuclear grade and large tumor burden (>2 cm) were significantly more common in breast cancer patients with BRCA1Mut carriers than those of BRCA2Mut carriers (OR: 2.663; 95% CI: 1.731–4.097; P = 0.211) or non-carriers (OR: 1.577; 95% CI: 1.067–2.331; P = 0.157). The data suggest that breast cancer patients with BRCA1Mut are more likely to have TNBC, high nuclear grade, and larger tumor burden.

Evaluation of association between degree of background parenchymal enhancement on MRI and breast cancer subtype

PurposeEvaluate possible association between BPE and breast cancer tumor type/prognostic markers. MethodsIRB approved retrospective study from 1/2010–1/2014 identified 328 patients who had breast MRI and available clinical/pathology data. BPE was categorized according to BI-RADS. The association between BPE and breast cancer molecular subtype/prognostic factors was evaluated. ResultsNo significant association was present between high BPE and the following: HER2+ tumors, basal tumors, tumors with axillary nodal disease, high nuclear grade tumors, high Ki-67 index tumors or larger tumors. ConclusionPatients with high BPE may be at increased risk for breast cancer but not necessarily for those cancer subtypes with a poor prognosis.

Value of computed tomography texture analysis for prediction of perioperative complications during laparoscopic partial nephrectomy in patients with renal cell carcinoma.

PurposeTumorous texture is a marker for tumor tissue inhomogeneity. Based on this assumption, this study aims to evaluate the value of computed tomography texture analysis for imaging-based prediction of perioperative complications during laparoscopic partial tumor nephrectomy.MethodsA total of 106 patients with histologically confirmed renal cell carcinoma and pre-operative CT were included and volumetric texture analysis of the tumors was performed by two readers. Texture analysis parameter ratios and differences were calculated using the kidney parenchyma as reference (“reference-corrected”). Regression analysis was performed, regarding the value of the texture analysis parameters, for assessment of the tumor nuclear grade and the prediction of peri- and postoperative complications and approximated blood loss. Moreover, the inter-rater agreement in terms of the intra-class correlation coefficient (ICC) was calculated.ResultsRegarding the reference-corrected values, the predictive value of texture analysis parameters for severe perioperative complications was highest for the standard deviation of the mean attenuation (Area under curve/AUC, .615; sensitivity, 93.8%, specificity, 30.0%), followed by the uniformity (AUC, .599; sensitivity, 62.5%, specificity, 60.0%), and the uniformity of distribution of positive pixels (AUC, .597; sensitivity, 62.5%; specificity, 61.1%).Regarding the blood loss, the uniformity of positive pixel values (UPP; AUC, 0.638), uniformity (AUC, 0.635), and entropy (AUC, 0.633) yielded the best predictive values, whilst the tumor grade was a weaker predictor (AUC, 0.574).The applied texture analysis parameters did not correlate with the time of surgery or the warm ischemic time. All measured parameters were better predictors for complications than the tumor diameter alone. The inter-rater agreement was almost perfect (ICC, .982).ConclusionCT and CT texture analysis parameters are valuable for prediction of perioperative outcome before laparoscopic partial nephrectomy in patients with renal cell carcinoma.

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals.

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I2 value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR=2.76, 95%CI: 2.25-3.38, I2=14.4%, P<0.001) and non-clear cell RCC (non-ccRCC) (HR=2.77, 95%CI: 1.62-4.72, I2=28.8%, P<0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR=1.76, 95%CI: 1.39-2.23; I2=56.3%), regional lymph node involvement (OR=2.10, 95%CI: 1.48-2.98; I2=14.9%), distant metastases (OR=2.69, 95%CI: 2.05-3.54; I2=0.0%), nuclear grade (OR=1.72, 95%CI: 1.32-2.23; I2=79.4%) and histologic tumor necrosis (OR=2.25, 95%CI: 1.59-3.18; I2=66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P=0.276) and the Egger's (P=0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.

Management of breast ductal carcinoma in situ in Catalonia, Spain: Results from the Grup Oncologic Calalà-Occità-Catalonia survey with 9-year follow up

IntroductionReliable data on DCIS incidence and management are not available in many countries. The present study describes the management of DCIS in Catalonia, Spain in the year 2005 and compares these findings to data obtained in France. Local recurrence and late toxicity rates from 2005 through the end of 2014 are reported. Materials and methodsObservational survey of patients with pure DCIS (n = 270) diagnosed during 2005. A written questionnaire, the same as used in the French survey, was completed by 14 doctors at 12 cancer centres in Catalonia, Spain. ResultsMedian patient age was 55 years (range, 29–89). Diagnosis was mammographic in 225 cases (83.3%). Treatment approaches included: mastectomy (10.4% of cases), breast-conserving surgery (BCS) alone (3.7%), and BCS plus radiotherapy (RT) (85.5%). Sentinel node biopsy and axillary dissection were performed in 27.4% and 5.6% of patients, respectively. Hormonotherapy was prescribed in 45.2% of cases. Tumour nuclear grade was as follows: low (16.7% of cases), intermediate (23%), and high (55.6%). Excision was complete (margins ≥1 mm) in 75% of patients treated with BCS alone vs. 95.7% for BCS+RT. The treatment approach varied widely: mastectomy rates ranged from 7.1% to 26.7% of centres, BCS+RT from 55.5% to 87.8%, and hormonotherapy from 3.3% to 83.3%. At a median follow-up of 102.6 months, 14 patients (5.6%) presented ipsilateral breast tumour recurrence. ConclusionsThese findings on DCIS management in Catalonia are consistent with previous international reports. The inter-centre differences observed are similar to those reported in other international surveys during the same period.

Prognostic Value of Vascular Endothelial Growth Factor A in the Prediction of the Tumor Aggressiveness in Clear Cell Renal Cell Carcinoma.

BACKGROUND:Clear cell renal cell carcinoma (CCRCC) is the most predominant renal tumour with unpredictable tumour behaviour. The aim of the study is to investigate the prognostic value of vascular endothelial growth factor A (VEGF-A) expression in CCRCC and to correlate it with other histological parameters as well as with patient’s survival.MATERIAL AND METHODS:Tumour blocks were taken from 40 patients with histopathology diagnosis of CCRCC and tissue block from 20 normal kidneys as a control group were examined using the immuno-histochemical staining for VEGF-A.RESULTS:The VEGF A expression in CCRCC was significantly higher than in the normal kidney tissues (U’ = 720, P < 0.0001). VEGF A expression values in CCRCC were positively correlated with Disease Free Survival (r = 0.335, P = 0.034) and the tumor necrosis degree (r = 0.181, P = 0.262). VEGF-A expression values in CCRCC did not correlate with CD 31 expression (r = -0.09, P = 0.549), and Progression Free Survival (r = -0.07, P = 0.838). VEGF A expression values in CCRCC were negatively correlated with the tumor nuclear grade (r = -0.161, P = 0.318); the pathological tumor stage (r = -0.371, P = 0.018); the tumor size (r = -0.361, P = 0.022); the degree of tumor hemorrhage (r = -0.235, P = 0.143); and Cancer Specific Survival (r = -0.207, P = 0.713).CONCLUSIONS:VEGF-A expression can be used to stratify advanced and metastatic CCRCC patients into low-benefit and high-benefit groups. Based on this study outcome it would be useful to perform IHC staining for VEGF-A expression in all patients with advanced and metastatic CCRCC.

Different expression patterns of histone H3K27 demethylases in renal cell carcinoma and bladder cancer.

UTX and JMJD3 are recently identified histone H3 lysine 27 (H3K27) demethylases. Many studies have shown aberrant H3K27 trimethylation (H3K27me3) levels widely exist in multiple cancers, and that altered H3K27me3 levels are correlated with tumorigenesis and tumor progression. To investigate expression patterns of UTX and JMJD3 genes in renal cell carcinoma (RCC) and bladder cancer and the relationship between gene expression and tumor development. Samples were collected from 35 patients with RCC and 21 patients with bladder cancer and qRT-PCR was performed. By comparing with adjacent normal tissues, the expression of JMJD3 (10/21 = 47.62%) and UTX (10/21 = 47.62%) were significantly upregulated in bladder cancer tissues and the expression of JMJD3 (15/35 = 42.86%) was significantly downregulated in RCC tissues. Stratified analyses revealed that upregulated expression of JMJD3 was significantly associated with poorly differentiated tumor nuclear grade (p= 0.005) and advanced clinical stage (p= 0.043) in the bladder cancer group, while downregulated expression of JMJD3 was significantly associated with advanced clinical stage (p= 0.045) and poorly differentiated tumor nuclear grade (p= 0.011) in the RCC group. These results suggest JMJD3 could be a hallmark and is involved in the development of RCC and bladder cancers. The potential role of H3K27 demethylases as biomarkers needs further investigations.

Abstract P3-17-03: DCIS and the risk of breast cancer death - A case control study

Abstract Introduction The risk of breast cancer death after a primary ductal carcinoma in situ (DCIS) is less than 2 % after 10 years. Whereas in situ recurrences do not influence survival, a 17-fold elevated risk of breast cancer specific mortality has been shown for invasive recurrences. Adjuvant radiotherapy (RT) effectively reduces recurrences after breast conserving surgery (BCS) for DCIS, but no studies have been able to demonstrate a survival benefit from adjuvant RT treatment or from choosing mastectomy instead of BCS. Here patient and tumour related risk factors for breast cancer death in women with a pure primary DCIS were studied. Patients and methods Women registered with a primary DCIS, between 1992-2012 in three of Sweden´s health care regions with a population of approximately 5.2 million, were enrolled in a nested case-control study. Out of 6,964 women with DCIS, 96 patients who later died from breast cancer were identified. Four controls per case (n=318) were randomly selected by incidence density sampling. We retrieved medical records and pathology reports and calculated OR with 95% CIs for various variables using conditional logistic regression. Results Of the 96 cases, 10 patients developed distant metastasis without a known local recurrence. In 56 patients death was preceded by an invasive ipsilateral recurrence and in 3 patients by a recurrent ipsilateral DCIS. Seven patients had invasive breast events in both the ipsilateral and the contralateral breast. Seventeen patients had contralateral invasive breast cancer and 3 patients contralateral DCIS. Multifocality and tumour size over 25mm (OR 2.6 (1.6 to 4.2)), positive or uncertain margin status (OR 2.8 (1.6 to 4.9)) and detection outside screening (OR 2.1 (1.2 to 3.9)) increased the risk of breast cancer death in univariate analysis, when adjusted for age and year of diagnosis. Suspicion of micro-invasion and nuclear grade 3 was associated with a nonsignificant increased risk, OR 1.8 (0.6 to 5.0) and 2.6 (0.9-6.5), respectively. The risk was not affected by age or treatment. Tumour size and margin status remained significant in the multivariable analysis, when adjusted for treatment and for contralateral breast cancer (OR 2.0 (1.2 to 3.7)). Conclusion In the present study, large tumours and positive or uncertain margin status were significant risk factors for later breast cancer death after a primary DCIS. More extensive treatment was not related to a lower risk. The significance of tumour biology and nuclear grade will be further examined and evaluated. Citation Format: Wadsten C, Garmo H, Fredriksson I, Sund M, Wärnberg F. DCIS and the risk of breast cancer death - A case control study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-03.