Clinicopathological Prognostic Parameters Research Articles

BRAF and TERT promoter mutations: clinical application in thyroid cancer.

Given the long-term survival of most patients with thyroid cancer, it is very important to distinguish patients who need aggressive treatment from those who do not. Conventional clinicopathological prognostic parameters could not completely predict the final outcome of each patient. Recently, molecular marker-based risk stratification of thyroid cancer has been proposed to better estimate the cancer risk. Although BRAF mutation has drawn much attention based on its high prevalence, its association with recurrence or mortality is not clear. Recently, telomerase reverse transcriptase (TERT) promoter mutation has been identified in thyroid cancer. It increases telomerase activity, which allows cancer cells to immortalize. It was found in 10 to 20% of differentiated thyroid carcinoma and 40% of dedifferentiated thyroid carcinoma. It is highly prevalent in old age, large tumor, aggressive histology, advanced stages, and distant metastasis. It is associated with increased recurrence and mortality. Concomitant BRAF and TERT promoter mutations worsen the survival rate. Inclusion of TERT promoter mutation analysis with conventional clinicopathological evaluation can lead to better prognostication and management for individual patients.

Histopathological and Clinical Features as Prognostic Factors of Atypical Meningiomas.

To analyze the correlation of clinicopathologic prognostic parameters with atypical meningiomas (AMs) and recurrence development as well as progression-free survival (PFS). The neuropathology archive and hospital records of 75 patients with AM who underwent surgery in our institution between 2010 and 2019 were retrospectively reviewed. The pathological revision was performed according to the 2016 World Health Organization (WHO) criteria. Other clinicopathological parameters, such as age, gender, tumor location, preoperative tumor size, degree of resection, Psammoma body, nuclear atypia, main histological pattern, Ki67 labeling index (LI), radiotherapy, and dura and bone invasion, were also analyzed. Statistically, univariate and multivariate analyses were assessed to determine their potential impact on recurrence-related prognostic factors. Recurrence occurred in 20 patients. The mean PFS and follow-up time were 38.9 and 44.8 months, respectively. In univariate analysis, clinical and pathological features such as age of ?55 years, female sex, skull base tumor location, larger preoperative tumor size, increased mitotic count, small cells, hypercellularity, sheeting, necrosis, and dura and bone invasion were remarkable in patients with recurrence, but were not statistically significant. In multivariate analysis, increased mitotic activity and brain invasion either considered alone or combined were significantly associated with PFS. Nuclear atypia was also not associated with both tumor recurrence and PFS. However, clinical features did not significantly influence the PFS. This study found that recurrence could not be predicted by the presence of any of the clinicopathological features of AMs. We believe that molecular variables determined through routine neuropathological analysis will be needed in the future.

Prognostic Impact of Adenosine Receptor 2 (A2aR) and Programmed Cell Death Ligand 1 (PD-L1) Expression in Colorectal Cancer.

Background Programmed cell death ligand 1 (PD-L1) is a key inhibitor to the immune response by binding to the specific receptor PD-1. Adenosine receptor 2 (A2aR) can play an immunosuppressive role in tumor microenvironment by binding to its ligand adenosine (ADO). However, the expression of these two markers has been rarely studied in colorectal cancer simultaneously. Materials and Methods We, respectively, collected tumor and adjacent nontumor tissue specimens of 204 patients with colorectal cancer. The expressions of PD-L1 and A2aR were detected by immunohistochemistry. The association among their expressions with clinicopathological characteristics and prognostic parameters were analyzed as well. Results The expressions of PD-L1 and A2aR in tumor tissues were both higher than those in matched adjacent nontumor tissues. PD-L1 expression was significantly correlated with lymph node metastasis and tumor TNM stage. A2aR expression was significantly correlated with tumor size, depth of tumor invasion, and TNM stage. Univariate analysis showed that the high expressions of PD-L1 and A2aR were inversely correlated with the overall survival, respectively. Multivariate analysis further confirmed that both of them were independent prognostic markers for patients. Conclusion The results of this study suggested that the high expressions of PD-L1 and A2aR were associated with a poor prognosis of colorectal cancer. Coinhibition of these two proteins may be a new breakthrough in the treatment of this disease.

EMT Markers in Locally-Advanced Prostate Cancer: Predicting Recurrence?

Background: Prostate cancer (PCa) is the second most frequent cause of cancer-related death in men worldwide. It is a heterogeneous disease at molecular and clinical levels which makes its prognosis and treatment outcome hard to predict. The epithelial-to-mesenchymal transition (EMT) marks a key step in the invasion and malignant progression of PCa. We sought to assess the co-expression of epithelial cytokeratin 8 (CK8) and mesenchymal vimentin (Vim) in locally-advanced PCa as indicators of EMT and consequently predictors of the progression status of the disease.Methods: Co-expression of CK8 and Vim was evaluated by immunofluorescence (IF) on paraffin-embedded tissue sections of 122 patients with PCa who underwent radical prostatectomies between 1998 and 2016 at the American University of Beirut Medical Center (AUBMC). EMT score was calculated accordingly and then correlated with the patients' clinicopathological parameters and PSA failure.Results: The co-expression of CK8/Vim (EMT score), was associated with increasing Gleason group. A highly significant linear association was detected wherein higher Gleason group was associated with higher mean EMT score. In addition, the median estimated biochemical recurrence-free survival for patients with < 25% EMT score was almost double that of patients with more than 25%. The validity of this score for prediction of prognosis was further demonstrated using cox regression model. Our data also confirmed that the EMT score can predict PSA failure irrespective of Gleason group, pathological stage, or surgical margins.Conclusion: This study suggests that assessment of molecular markers of EMT, particularly CK8 and Vim, in radical prostatectomy specimens, in addition to conventional clinicopathological prognostic parameters, can aid in the development of a novel system for predicting the prognosis of locally-advanced PCa.

Epidermal growth factor receptor (EGFR) overexpression in triple-negative breast cancer: association with clinicopathologic features and prognostic parameters

IntroductionTriple-negative breast cancers are a poor prognostic group of breast cancers that don’t respond to conventional hormonal and her2neu targeted therapy. A subset of triple-negative breast cancer is known to overexpress epidermal growth factor receptor (EGFR); however prognostic significance of this biomarker has not been widely studied in our population. Therefore, we aimed to evaluate the frequency of EGFR overexpression in triple-negative breast cancer in our setup and its association with prognostic and predictive factors.MethodsWe performed EGFR immunohistochemistry on 150 cases of triple-negative breast cancers. Intensity and percentage of EGFR expression were combined to formulate an EGFR score, that was compared with prognostic features of breast cancer and recurrence status of patients.ResultsPositive EGFR expression was noted in 18.7% ( 28 cases); out of which 16% (24 cases) showed low EGFR expression, whereas high EGFR expression was seen in 2.7% ( 4 cases). No significant association of EGFR expression was noted when compared with various clinicopathological parameters and recurrence status of the patients.ConclusionWe found EGFR protein expression in 18.7% of cases while high expression was seen in only 2.7 % cases of triple-negative breast cancer which may harbor underlying genetic alterations like altered EGFR gene copy number, chromosome 7 copy number or average EGFR gene: chromosome 7 ratio; therefore we suggest that molecular tests like FISH to evaluate these EGFR molecular alterations should be performed in EGFR over expressing triple negative breast cancers in our setup to identify patients that can benefit from anti-EGFR targeted therapy. Moreover, regional difference in EGFR expression (high expression in chinese population compared to our population) are may be due to different underlying genetic alterations in triple-negative breast cancers, further necessitating a need of devising personalized therapeutic protocols for locoregional population.

Is there a patient population with squamous cell carcinoma of the head and neck region who might benefit from de-intensification of postoperative radiotherapy?

The aim of this retrospective study was to evaluate the clinical outcome of apreviously defined low-risk patient population with completely resected (R0) squamous cell carcinoma of the oral cavity, oropharynx, larynx (pT1-3, pN0-pN2b), hypopharynx (pT1-2, pN0-pN1), and the indication for postoperative radio(chemo)therapy. According to predefined criteria, 99patients with head and neck squamous cell carcinoma (SCC) who were treated at our institution from January1, 2005 to December31, 2014, were available for analysis. The Kaplan-Meier method was used for calculating survival and incidence rates. For univariate comparative analysis, the log-rank test was used for analyzing prognostic clinicopathologic parameters. Median follow-up was 67months. Cumulative overall (OS) and disease-free survival (DFS) were 97.9%/94.7%/88.0% and 96.9%/92.6%/84.7% after 1, 2, and 5years, respectively. Cumulative incidence of loco-regional recurrence (LRR), distant metastases (DM), and second cancer (SC) were 1.0%/1.0%/4.9%, 0.0%/3.4%/5.8%, and 2.1%/4.2%/13.1%, respectively. In univariate comparative analysis, location of the primary tumor in the oropharynx was asignificant predictor for increased OS (p = 0.043) and DFS (p = 0.048). Considering the low disease relapse rates and high rates of therapy-induced late side effects, as well as the increased risk of developing SC, aprospective multicentric trial investigating de-escalation of radiotherapy in this clearly defined low-risk patient population was started and is still recruiting patients (DIREKHT-Trial, NCT02528955).

Assessment of the concordance between fluorescence in-situ hybridization and immunohistochemistry in evaluating topoisomerase IIα in breast carcinoma

Background Topoisomerase IIα (TOP2A), encoded by TOP2A gene, is a molecular target for anthracycline therapy; hence, it can serve as a predictive or prognostic factor. There are several techniques used for measuring TOP2A status. The relative value of TOP2A gene amplification evaluated by fluorescence in-situ hybridization (FISH) and protein expression analyzed by immunohistochemistry (IHC) is yet unclear in the literature. Aim To evaluate the concordance between FISH and IHC for TOP2A status and to assess their relations with some prognostic clinicopathological parameters. Materials and methods A total of 86 invasive breast cancer paraffin blocks were retrieved from the archives of Pathology Department, National Cancer Institute, Cairo University, and were subjected to IHC, with a cutoff value of 10%, and FISH analysis with TOP2A/centromere enumeration probe 17 ratio of at least two for TOP2A expressions. The concordance between the results of both techniques as well as relations with selected prognostic parameters was evaluated. Results Of 86 invasive breast carcinomas, 43 (50%) revealed TOP2A protein overexpression, whereas 23 (26.7%) cases had TOP2A gene amplification. TOP2A gene amplification was recognized in 16 of 43 TOP2A protein-expressed cases, with 37.2% concordance rate and 0.209 κ statistics. TOP2A gene amplification was significantly correlated with human epidermal growth factor receptor-2 immuno-expressing tumors and with molecular subtypes (P Conclusion Discordance was evident between TOP2A gene amplification and protein expression. However, TOP2A gene amplification has a valuable prognostic influence, whereas protein expression is still a predictive factor useful to guide chemotherapy.

Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy.

Programmed death-ligand 1 (PD-L1), a potential target for immune checkpoint inhibitors in various solid neoplasms, has been studied in very few cases of Gall Bladder Carcinoma (GBC). The current study aimed to evaluate PD-L1 expression at primary and metastatic sites of GBC, and its associations with standard prognostic clinicopathological parameters, as well as with overall survival. One hundred and seventy-four cases of GBC were evaluated for PD-L1 expression by the use of the SP263 clone in tissue microarrays. Clinicopathological characteristics and survival data were correlated with PD-L1 expression analysed at different cut-offs of ≥1%, ≥10% and ≥50% in tumour cells and tumour-infiltrating lymphocytes (TILs). The mean age of patients was 49.9 years, and the male/female ratio was 1:2.9. Of the cases, 73.6% presented with stage 3/4 disease. Tumour cells expressed PD-L1 in 23.0% of cases, and TILs expressed PD-L1 in 24.1% of cases. At a cut-off of 10%, 14.9% of cases expressed PD-L1, and at a cut-off of 50%, 7.5% of cases expressed PD-L1. Significant associations were seen between tumour proportion score and histological type (P = 0.004), histological grade (P = 0.004), nuclear grade (P = 0.008), nodal metastasis (P = 0.051), higher stage (P = 0.058), and TILs (P < 0.001). Tumour size, growth pattern, the presence of necrosis and lymphovascular emboli showed no significant associations with PD-L1 in tumour cells or TILs. In synchronous paired samples from primary and metastatic lymph nodes, discordantly higher PD-L1 expression was evident in lymph nodes. Overall survival was not associated with PD-L1 expression (P = 0.546). PD-L1 does not appear to be a prognostic marker or influence survival in GBC patients. However, PD-L1 expression occurs in one of four GBCs, supporting the future possibility of immune-modulation therapy to improve the dismal overall survival.

Clinicopathologic features and prognosis of inflammatory pseudotumor-like follicular dendritic cell sarcomas in liver and spleen: an analysis of seven cases

Objective: To investigate the clinicopathological features and prognostic parameters of the inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) of liver and spleen. Methods: Ninteen cases of inflammatory pseudotumor (IPT) and 5 cases of IPT-like FDCS of the liver and spleen were collected at the First Affiliated Hospital, Army Medical University from 2006 to 2016. HE sections, immunohistochemical staining, and Epstein-Barr virus encoded nuclear RNA (EBER) in situ hybridization were reviewed along with a summary of the literature. Results: Among the previously diagnosed 19 cases of IPT of the liver and spleen, 2 cases were misdiagnosed (the ratio of 2/19). Among 7 new cases including 3 males and 4 females, 3 cases involved the liver and 4 cases involved the spleen. The age range was 37-64 years (mean 53 years). The maximum tumor diameter ranged from 3.0 to 11.0 cm (mean 6.5 cm). Surgical resections were performed in all patients with follow-up time ranging from 3 to 84 months.All patients were disease-free.7 new cases were all positive for EBER, and showed the expression of at least one of the FDC markers, including CD21, CD23, and CD35. The rest of 17 cases of IPT were all negative for EBER and essentially negative for FDC markers, but were all positive for SMA. Conclusions: IPT-like FDCS of the liver and spleen is a rare low-grade malignant tumor morphologically mimicking inflammatory pseudotumor, and is easy to be misdiagnosis due to under-recognition. EBER in situ hybridization and FDC markers are indispensable for confirming the diagnosis.

Correlation of proliferative index with various clinicopathologic prognostic parameters in primary breast carcinoma: A study from North India.

Routine assessment of cell proliferation is recommended in the pathologic evaluation for all breast cancers. Considering the poor reproducibility and interobserver variability in mitotic counts, Ki-67 is an easily available and reliable substitute for mitotic counts and has been shown to have a significant relationship with the histologic grade of malignancy and the mitotic activity of tumors. Our study aimed at exploring Ki-67 expression and studying its correlation with other established prognostic parameters. Seventy-five cases of primary breast cancer undergoing radical or modified radical mastectomy constituted the study group. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, and Ki-67 was assessed in each case. Ki-67 labeling index (Ki-67-LI) was estimated as the number of positive nuclei divided by total number of nuclei scanned counting a minimum of 1000 cells in 10 selected high power fields that displayed the highest immunoreactivity and was expressed as percentage. Ki-67 expression was correlated with various clinicopathologic prognostic parameters including age, tumor size, tumor type, axillary lymph node status, and histologic tumor grade. A statistically significant direct association was observed between Ki-67-LI and tumor size, histologic grade and Nottingham prognostic index. A statistically significant inverse association was observed between Ki-67-LI and ER and PR expression. However, no association was observed between Ki-67-LI and menopausal status, lymph node involvement and HER2/neu expression. Based on our results, we concluded that modified Bloom-Richardson (MBR) grading has been recognized as a treatment related indicator. The accuracy and reliability in grading have always been a matter of concern, hence, the reproducibility of grading should be enhanced. Ki-67-a proliferation marker is easily identified and provides comparable accurate information. In contrast to poor reproducibility of mitotic counts, Ki-67 can achieve high agreement between pathologists; is more reproducible; adds complementary value to the MBR grading system and correlates well with other clinicopathologic parameters. It may act as a significant prognostic indicator for routine clinical use and be helpful for selection of adjuvant treatment. It can also add value in categorizing Grade II tumors into two prognostic subgroups with prognosis equivalent to Grades I and III, respectively.

COX-2 Expression in Breast Carcinoma with Correlation to Clinicopathological Parameters

ObjectiveBreast carcinoma is the most common malignant tumor and the leading cause of carcinoma deaths in women. Its etiology is multifactorial, implicating reproductive factors, hormonal imbalances and genetic predispositions. Studies have shown that Cycloxygenase-2 (COX-2) plays an important role in the carcinogenesis and increased expression has been regarded as a poor prognostic factor. The objective of our study is 1. To study COX-2 expression in normal breast tissue, DCIS and invasive breast cancer. 2. To determine COX-2 expression with clinicopathological prognostic parameters.MethodsRadical mastectomy specimens were studied for COX-2 expression by immunohistochemistry in 50 patients diagnosed as breast carcinoma. COX-2 expression is quantified as IHS Score and separately calculated for normal breast epithelium near the tumor, DCIS and invasive areas. Relationship between COX-2 expression with various clinicopathological parameters was evaluated.ResultThe results of our study suggest an association of the expression of COX-2 to the factors associated with poor prognosis in breast cancer, such as larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. There was a higher COX-2 expression in the DCIS component as compared to the invasive ductal carcinoma component and the adjoining breast epithelium.ConclusionOur study established the role of COX-2 in carcinogenesis and its association with adverse prognostic factors.

ABO Blood Group and Endometrial Carcinoma: A Preliminary Single-Center Experience from Saudi Arabia.

Introduction: Inherited ABO blood groups have been shown to play possible contributions in the pathogenesis of various gynecologic and non-gynecologic carcinomas. With regard to gynecologic carcinomas, there is a confined number of studies that explored the relationship between ABO blood group and endometrial carcinoma (EC) in the PubMed-indexed literature. To the best of our knowledge, no such study has ever been conducted in Saudi Arabia.Objectives: Our study has two objectives: (I) to determine the prevalence of ABO blood groups among Saudi patients with EC, and (II) to explore the relationship between ABO blood group and several clinico-pathological prognostic parameters (namely: menopausal status [age], body mass index [BMI], tumor grade, FIGO [Fédération Internationale de Gynécologie et d'Obstétrique] stage and recurrence) in Saudi patients with EC.Materials and Methods: A retrospective cross-sectional study from 01-January-2010 to 31-July-2014 was conducted at King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia — a referral tertiary healthcare institute. One-hundred and fourteen patients (n=114) were included in the study. Clinico-pathological data were extrapolated from medical records, and their association with ABO blood groups were evaluated. Categorical data were presented as number of cases (n) and percentages (%). Two-tailed Chi-square test was used for univariate analysis. For all purposes, p values <0.05 were regarded as statistically significant.Results: The mean age and BMI were 59.5 ± 10.8 years (range: 31 – 90) and 36.6 ± 8.6 kg/m2 (range: 17 – 60), respectively. The vast majority of patients were post-menopausal (86%), had BMI >28 kg/m2 (84.2%), diagnosed with early FIGO stage I-II (76.3%) and developed no recurrence (86.8%). The frequencies of ABO blood group types A, B, AB, and O were 28.1%, 12.3%, 3.5% and 56.1%, respectively. When ABO blood groups were analyzed as four different types (A, B, AB and O), O-type was the most common ABO blood group in pre- and post-menopausal EC patients (43.8% and 58.2%, respectively; p=0.14). There were no statistically significant correlations between ABO blood groups and all the examined clinico-pathological factors. Moreover, when ABO blood groups were analyzed as two different types (O and non-O), similar results were obtained; no statistically significant correlations were found between ABO blood groups and all the examined clinico-pathological factors.Conclusions: O-type was the most prevalent ABO blood group among Saudi Arabian patients with EC, and our finding was different from the existing literature, probably highlighting an ethnic-related variance. Furthermore, no statistically significant correlations were identified between ABO blood groups and all the examined clinico-pathological factors. Also, routine ABO blood group may emerge as a clinically accessible, beneficial and economical biomarker for a possible EC vulnerability. A large-sized case-control study is needed to withdraw solid conclusions.

520P - AMALTHEA: A prospective, single-arm study of the Hellenic Cooperative Oncology Group evaluating the efficacy and safety of 1st line FOLFIRI+Aflibercept in patients with metastatic colorectal cancer

Background: The efficacy and safety of the FOLFIRI regimen combined with aflibercept has not been studied in the first-line management of patients with metastatic colorectal cancer (mCRC). Methods: In the context of a prospective single-arm trial, patients with mCRC received standard doses of Leucovorin, 5-Fluorouracil and Irinotecan (FOLFIRI) combined with aflibercept (4 mg/KBW iv) every 2 weeks until disease progression, unacceptable toxicity or completion of 12 cycles, followed by aflibercept maintenance. Endpoints were the 12-month Progression-Free Rate (PFR12), efficacy and toxicity. Results: 73 fit patients were enrolled in the study between 2014 and 2016. Fifty-five patients had tumors in the left colon, forty-four presented with synchronous metastases. Median relative dose intensities administered were 0.85 (95% CI 0.74-0.84) for 5-FU CI, 0.80 (95% CI 0.73-0.89) for Irinotecan and 1.0 (95% CI 0.92-0.98) for Aflibercept. In total, adverse events occurred in 70 patients (95.9%), with no toxic deaths. The most common grade 3 or 4 adverse events were neutropenia (13 patients, 18%), febrile neutropenia (3 patients, 4%), diarrhoea (11 patients, 15%), hypertension (19 pts, 26%), proteinuria (8 pts, 11%), infections (8 pts, 11%), mucositis (6 pts, 8%). Among 85 adverse events of special interest (AESI) observed, 57 events ended with complete recovery. Among eight patients with severe proteinuria, improvement to grade 0/2 occurred in six at a median time of 4.8 months. The Objective Response Rate (ORR) was 46.6% in the ITT population (n = 73) and 51.5% in the evaluable population (n = 66). Among potential prognostic clinicopathological parameters (including RAS, BRAF status, primary site), the presence of synchronous metastases and a relapse-free interval <12 months were significantly associated with response (odds ratio 2.92 and 3.75 respectively), while a performance status of 0 with overall survival (hazard ratio 0.42). At a median follow-up of 20.9 months, the median OS was 24.7 months (95% CI 17.3-30.5), the median PFS 8.4 months (95% CI 7.44-9.44), while the 12-month PFS rate was 21.8%. Conclusions: The FOLFIRI + Aflibercept regimen is active and safe, however it failed to improve historical benchmarks of efficacy in chemonaive patients with mCRC. Clinical trial identification: EudraCT No.: 2013-002567-26 Legal entity responsible for the study: Hellenic Cooperative Oncology Group (HeCOG) Funding: Sanofi-Aventis Disclosure: V. Karavasilis: Advisory Board: Novartis, Roche, Astellas, Merck, Sanofi, Pfizer, Astra-Zeneca, Janssen. Honoraria: Novartis, Roche, Astellas, Merck, Sanofi, Pfizer, Astra-Zeneca, Janssen. G. Aravantinos: Honoraria: Genesis pharma SA Scientific Advisory Board: Amgen, Astra-Zeneca, BMS, GSK, Roche, Sanofi. I. Souglakos: Honoraria: Sanofi. Research grant: Sanofi. G. Fountzilas: Honoraria: Astra-Zeneca. Consulting or Advisory Role: Pfizer, Sanofi, Roche. Stock and other ownership interests (an Immediate family member): Ariad. All other authors have declared no conflicts of interest.

Diagnostic Utility of Thyroid Transcription Factor-1 in Ovarian Carcinoma and Its Relationship With Clinicopathologic Prognostic Parameters.

Although thyroid transcription factor-1 (TTF-1) is considered a relatively sensitive and specific marker for lung and thyroid neoplasms, it can occasionally be expressed in other tumors. Few immunohistochemical studies have been conducted on TTF-1 expression in ovarian carcinomas with discrepant results. To date, only 1 study compared different TTF-1 clones in ovarian carcinoma. This study is designed to evaluate the expression of TTF-1 clones in ovarian carcinomas and investigate TTF-1 association with clinicopathologic prognostic parameters. A retrospective immunohistochemical study was conducted on 62 primary ovarian carcinomas and 15 normal ovarian tissues using 2 clones of TTF-1 antibody (SPT24 and 8G7G3/1). Nuclear expression of SPT24 and 8G7G3/1 clones of TTF-1 was detected in 17.7% and 3.2% of ovarian carcinomas, respectively. Positive cytoplasmic immunostaining of clone SPT24 was detected in 1.6% of cases. In contrast, normal ovarian tissue showed negative expression of both clones. A highly significant difference was observed between both clones regarding their sensitivity in ovarian carcinomas (P=0.004). A significant inverse relationship was observed between TTF-1 (SPT24 clone) expression and tumor stage (P=0.022). TTF-1 expression is not exclusive to lung and thyroid tissue. It is expressed in ovarian carcinomas where clone SPT24 is more sensitive than clone 8G7G3/1. TTF-1 might be of diagnostic utility in evaluating neoplasms of unknown primary origin as well as adenocarcinomas involving the lung in patients with a history of a gynecologic malignancy. Moreover, TTF-1 expression might be a good prognostic factor in ovarian carcinoma.

Immunohistochemical determination of estrogen and progesterone receptors in breast cancer: relationship with clinicopathologic factors in 302 patients in Ivory Coast

BackgroundBreast cancer is a heterogeneous and a hormone-dependent disease. The detection of the estrogen receptor (ER) and progesterone receptor (PgR) is crucial for prognostic evaluation and treatment choice of breast cancer for clinical practice. The purpose of this study was to evaluate the expression of the hormonal receptors, their distribution, and their correlation with clinicopathologic prognostic parameters for the improvement of the patients’ treatment in Ivory Coast.MethodsThe 20-month prospective study included 302 patients who were diagnosed with primary invasive breast carcinomas at the Central Laboratory in Abidjan. The paraffin-embedded blocks of these patients were examined by immunohistochemistry to assess the ER and PgR status. The one-way analysis of variance and Chi-Square Test were used to analyze the data.ResultsThe mean age of patients at diagnosis was 48 ± 11 years. The majority of the women were premenopausal in 180 cases (59.9%). The predominant histologic type was invasive ductal carcinoma not otherwise specified (IDC NOS) in 247 cases (82%). Tumor grade 2 was more frequent in 166 cases (55%). Among 302 patients, 169 (56%) and 154 (49%) expressed ER and PgR respectively. The ER+PgR+ group with 131 cases (43%) was predominant, followed by 116 cases (38%) of ER-PgR-. The expression of ER and PgR was correlated with the age of the patients (p = 0.026) and the tumor grade (p = 0.0004). However, there was not statistically significant correlation between ER/PgR and the menopausal status of patients (p = 0.149), nor between ER/PgR and the histologic type (p = 0.523).ConclusionThe ER+PgR+ and ER-PgR- are the most common subgroups in women with breast cancer in Ivory Coast. The hormonal receptor status is associated with the age and the histologic grade in breast cancer patients. The systematic use of hormonal treatment should be reevaluated. A further study should be done to investigate the reasons of high rate of ER-PgR- in breast cancer patients in Ivory Coast.

The Correlation of Tissue-Based Biomarkers in Primary and Metastatic Renal Cell Carcinoma Lesions: A Tissue Microarray Study

Purpose The study was aimed to determine the correlations of tissue-based biomarker expressions between primary and metastatic specimens of renal cell carcinoma and with several well-known prognostic clinicopathological parameters. Materials and Methods The immunohistochemistry (IHC) was used to determine the expression levels of 9 tissue-based markers calculated in H-score expressed by percentage of expression multiplied by the intensity score (0, 1, 2, and 3 points). Using 17 patients' 38 specimens paired with primary renal lesion and its metastatic lesions collected between 2004 and 2015, Tissue microarray with IHC was performed with BAP1, PBRM1, pS6, PTEN, TGase2, PD-L1, CA9, PSMA, and Ki-67 on formalin-fixed paraffin-embedded sections. Pearson correlation and accuracy test were performed to analyze the correlation between primary and metastatic tissues. Results The 17 patients' mean age was 56.9 years old, mean tumor size was 7.9 cm, and the male to female ratio was 13:4 (76.5%:23.5%), respectively. Three patients had 2, 3, and 3 metastatic tissues, and the rest of 14 patients had only one metastatic tissue. The H-score (PSMA and Ki67) and intensity score (pS6 and PSMA) showed that some differential significant markers were identified which had statistical correlations of expression levels between primary and metastatic lesions among 9 markers. However, no real correlation of PSMA, Ki67, and pS6 markers were found their expressions of between primary and metastatic tissues because of their skewed expressions. Conclusions Tissue markers failed to correlate their expression levels in primary lesions with those of metastatic lesions. Key Words: Renal cell carcinoma; Metastasis; Tissue microarray; Biomarker; Immunohistochemistry.

English

BACKGROUND : Carcinoma of the breast has clinical heterogeneity with high morbidity and mortality. Determination of prognostic factors is important in improving the overall survival breast cancer patients. Her2/neu is one of the powerful predictors of poor prognosis. Thus a study of Her2/neu expression estimated by immunohistochemistry in breast cancer is the need of the hour. This study investigates correlations between the presence of Her2/neu and various clinicopathological prognostic parameters in primary breast carcinomas. OBJECTIVES : 1. Study of the HER2/neu status in breast carcinomas in the study sample. 2. To find the association of HER2/neu status with clinicopathological prognostic parameters in breast carcinomas in the study sample. 3. To find the association of HER2/neu status with lymph node status. METHODOLOGY : Patients diagnosed as carcinoma breast, admitted in Department of General surgery, Govt. Royapettah Hospital and post operative modified radical mastectomy specimens were examined for gross and microscopic features. Immunohistochemistry was used to study the Her2/ neu expression. Her2/neu status was correlated with various clinicopathological prognostic parameters. RESULTS : There was a significant statistical association between Her2/neu expression with lymph node status(p=0.012) and presenting symptoms such as pain and nipple discharge. Expression of Her2/ neu expression was increased in tumour size of more than 2 cms (64%) and higher tumour grade (90%). The major histological subtype was Infiltrating duct carcinoma, NOS type. Meanwhile there was no significant association of Her2/neu expression with menopausal status, NPI groups and other histological parameters. CONCLUSION : Our study data indicates that Her2/neu may be a more powerful predictor for poor prognosis as its expression is associated with important prognostic parameters like increased tumour size, high tumour grade, high NPI score and lymph node involvement.

Prognostički značaj morfologije invazivne tumorske fronte u karcinomu pločastih stanica usne

Aim: To establish invasive tumor front grade (ITFG) in squamous cell carcinoma of the oral cavity (OCSCC), compare it with traditional histological grade and to investigate the prognostic value of both. Materials and methods: The whole tumor-tissue sections, stained with HE of 86 OCSCC cases were evaluated for the invasive tumor front grade and compared with the clinicopathological prognostic parameters such as pathological stage (pT stage), pathological lymph node stage (pN stage), clinical stage (TNM stage) and length of survival of patients. Tissue has been disposed at the Department of Maxillofacial Surgery, University Hospital Rijeka. Data of traditional histological grade were obtained from previous histological findings. Results: Traditional histological grade was not significantly associated with clinical parameters or survival of patients (P = 0.906). High ITFG was associated with positive lymph nodes (P = 0.006) and clinical stage of disease (P = 0.025), but not to pathological T stage (P = 0.086). In univariate analysis high ITFG was associated with shorter survival of patients (P = 0.001), and multivariate analysis showed it as the independent prognostic factor (P = 0.006). For individual parameters that determine ITFG like inflammatory infiltrate, way of invasion and degree of keratinization was also established statistically significant prognostic value in univariate (P < 0.001, P = 0.013, i.e., P = 0.009) and multivariate analysis. Conclusion: ITFG has greater prognostic value than the traditional histological grade. Determination of ITFG may help identify patients with a higher risk of disease recurrence after surgical removal of the tumor, which would use additional methods of treatment.

Intra-patient Inter-metastatic Genetic Heterogeneity in Colorectal Cancer as a Key Determinant of Survival after Curative Liver Resection.

Chromosomal instability is a well-defined hallmark of tumor aggressiveness and metastatic progression in colorectal cancer. The magnitude of genetic heterogeneity among distinct liver metastases from the same patient at the copy number level, as well as its relationship with chemotherapy exposure and patient outcome, remains unknown. We performed high-resolution DNA copy number analyses of 134 liver metastatic deposits from 45 colorectal cancer patients to assess: (i) intra-patient inter-metastatic genetic heterogeneity using a heterogeneity score based on pair-wise genetic distances among tumor deposits; and (ii) genomic complexity, defined as the proportion of the genome harboring aberrant DNA copy numbers. Results were analyzed in relation to the patients’ clinical course; previous chemotherapy exposure and outcome after surgical resection of liver metastases. We observed substantial variation in the level of intra-patient inter-metastatic heterogeneity. Heterogeneity was not associated with the number of metastatic lesions or their genomic complexity. In metachronous disease, heterogeneity was higher in patients previously exposed to chemotherapy. Importantly, intra-patient inter-metastatic heterogeneity was a strong prognostic determinant, stronger than known clinicopathological prognostic parameters. Patients with a low level of heterogeneity (below the median level) had a three-year progression-free and overall survival rate of 23% and 66% respectively, versus 5% and 18% for patients with a high level (hazard ratio0.4, 95% confidence interval 0.2–0.8, P = 0.01; and hazard ratio0.3,95% confidence interval 0.1–0.7, P = 0.007). A low patient-wise level of genomic complexity (below 25%) was also a favorable prognostic factor; however, the prognostic association of intra-patient heterogeneity was independent of genomic complexity in multivariable analyses. In conclusion, intra-patient inter-metastatic genetic heterogeneity is a pronounced feature of metastatic colorectal cancer, and the strong prognostic association reinforces its clinical relevance and places it as a key feature to be explored in future patient cohorts.

A dual prognostic role for the TGFβ receptors in human breast cancer

The transforming growth factor-β (TGFβ) plays a dual role in breast cancer, acting as a tumor suppressor in early carcinomas while promoting tumor metastasis in more advanced breast carcinoma. As a result, the prognostic role of TGFβ and its signaling components in breast cancer remains unclear. Here we evaluated the expression levels of TGFβ signaling receptors TβRII and TβRI using human breast cancer tissue microarrays and a large publicly available gene profiling database in relation to various clinicopathological parameters. Our results indicate that breast cancer tissues express lower TβRII and TβRI protein levels compared with normal breast tissue. In contrast to TβRI expression, TβRII mRNA expression levels were also significantly downregulated in invasive breast cancer compared with normal breast tissue (4.18-fold downregulation, P=9.3×10-115). Interestingly, within the cancer cases analyzed, our results revealed a direct correlation between high TβRII and TβRI expression levels and classic poor prognostic clinicopathological parameters, including larger tumor size, advanced tumor stage, and poorly differentiated tumors. Next, we examined TGFβ receptors' expression in relation to breast cancer molecular subtypes. Importantly, our results revealed that whereas expression of TGFβ receptors in luminal A and triple-negative breast cancer showed no correlation with patient outcome, their expression in luminal B and HER2 subtypes showed significant association with favorable patient outcome. Together, these results indicate that although TGFβ receptors are downregulated in breast cancer, their expression in tumors is an indicator of aggressive breast cancer phenotype. Moreover, the relation between TGFβ pathway and patient outcome is breast cancer subtype dependent.