Introduction: The aim of this study was to determine whether radiomic features measured at baseline in Magnetic Resonance images (MRI) of acoustic neuromas (AN) can predict Gamma Knife (GK) treatment outcome.
Methods: The study was conducted on pre- and post-GK MRI-T2 scans of 32 patients with AN who underwent stereotactic radiosurgery (SRS) for 12 Gy dose. Radiomic features extracted include Intensity, Fractals, Laplacian of Gaussian and textural Co-Occurrence, Run-length (RL), Size Zone, and Neighborhood Gray-Tone Difference matrices (NGTDM) features. Subjects were classified as treatment failures (TF) if tumor volume increased > 10%. Pre- and post-SRS audiology reports were utilized in hearing evaluation.
Results: Fifteen subjects (47%) qualified as TFs. In univariate receiver operating characteristic (ROC) analysis, two radiomic features, complexity in NGTDM and run percentage in RL, displayed areas under curves of > 0.65.
Conclusion: This initial radiomic study establishes features that illustrates the prognostic ability of the SRS treatment in acoustic neuroma. Hearing preservation was achieved in a majority of acoustic neuroma patients treated in Gamma Knife.
Introduction: To check the impact of the clinical and pathologic features at diagnosis and treatment given, on the outcome of synovial sarcoma in children and adolescents.
Methods: Retrospective analysis of patients below 18 years old diagnosed by synovial sarcoma and treated at Children Cancer Hospital Egypt 57,357 (CCHE) between July 2007 and December 2016. We reviewed Clinical characteristics, pathological information, treatment modalities and survival data.
Results: We included thirty one patients with median age at diagnosis was 14.8 years. Initial surgical excision was possible in 10 patients (58.8%) while 5 (29.4%) patients underwent surgical excision after response to preoperative chemotherapy. Two patients had unresectable tumor, showed no response to chemotherapy and received radiotherapy as the only local control therapy. Adjuvant radiotherapy only was given in 2 patients and 5 patients received chemotherapy without local radiotherapy and 10 patients received both modalities. The estimated 5-year overall survival and failure free survival rates for the entire group were 84.4% ± 7.2% and 63.8% ± 9.7% respectively, the 5-year OS and FFS were studied in correlation to age of patient, tumor size, different pathological types, site of the lesion and methods of local control. In patients with tumor size below 5 cm when compared to size more than 5 cm with OS was (100%) in comparison to (79.3 ± 9.3) who underwent complete surgical excision either initial or post chemotherapy as it was 66.7% versus 55.6% for those with gross or microscopic residual (p-value =.38). Also, the 3-year failure free survival was 75% versus 56.3% for those smaller than or equal 5 cm and those larger than 5 cm respectively (p-value =.3).
Conclusion: Increasing number of patients to increase sample size to assess tumor size and complete surgical excision as important prognostic factors as in our study, we found them statistically insignificant. Preoperative chemotherapy can help for delayed excision in patients presented initially with unresectable tumors
Background: The pathogenesis of non-Hodgkin lymphoma is a complex process that involves several molecular changes. Alterations in polycomb group proteins as well as Survivin have been described but details are still lacking particularly in T/NK-cell lymphomas. Polycomb proteins have a big role in cell cycle and differentiation. Survivin is another recently recognized player in non-Hodgkin lymphoma.
Objective: To study the pattern of Bmi-1 and Survivin in different categories of B- and T/NK- cell non-Hodgkin lymphomas, their association with the clinicopathological parameters, and their impact on the prognosis of non-Hodgkin lymphomas.
Material& methods: Immunohistochemical staining was used to study paraffin samples of 267 patients’ biopsies. We used tonsils and reactive lymph node as normal control.
Results: Both Bmi-1 and Survivin showed significant upregulation in several subtypes B- (P =.000-.02 for Bmi-1 and.00-.03 for Survivin) and T/NK cell lymphomas (P=.009-.03 for Bmi-1 and 0.008- 0.009 for Survivin) compared to normal tissue. Significant positive correlation between Bmi-1 and Survivin was detected in both B- (Co= 0.539**, P =.00) and T - cell lymphomas (Co= 0.560**, P =.000). A statistically significant difference between overall survival and expression of both BMI-1 and Survivin was detected (P =.00 for BMI-1and survivin).
Conclusion: Bmi-1 and Survivin show significant upregulation as well correlation with clinicopathological parameters and overall survival of non-Hodgkin lymphomas.
Macrophages are the first line of defense in the cellular environment in response to any antigenic or foreign invasion. Since cancer cells express antigenic molecules and create a tumor microenvironment quite different from the normal cellular environment, macrophages will attack this cancer cells as foreign Invaders. However, the cancer cells adept their ability to suppress macrophage activity by secreting compounds/proteins through unknown mechanisms and train these macrophages to aid in tumorigenesis. These macrophages are commonly known as tumor associated macrophages (TAM). In this study, our goal was to find out key regulatory molecules involved in this conversion of cancer-fighting macrophages to cancer friendly macrophages. We used African American(AA) patient derived established human prostate cancer cells along with the human derived macrophages followed by Affymetrix cDNA microarray analysis. Microarray analysis of the PCa cell exposed macrophages revealed appreciable decrease in mRNA expression of several genes associated with phagocytosis process. Aberrant expression of several noncoding RNAs that control the expression of such phagocytosis associated molecules were also evident. Increased expression of oncogenic miR such as, miR-148, 615, 515, 130, 139 and markedly decreased expression of tumor suppressive miR’s MiR-3130, let7c,101,103, 383 were noted. Further, TARGET SCAN analysis demonstrated these differential expression of non-coding RNA’s causing down regulation of phagocytosis promoting genes elf5A, Meg3, Tubb5, Sparcl-1, Uch-1, Bsg(CD147), Ube2v, GULP, Stabilin 1 and Pamr1. There is an increase of RAP1GAP gene that causes concomitant decrease in the expression of tubulin genes that promote cytoskeletal assembly in forming phagosomes. In addition Ingenuity pathway analysis of the gene expression data also showed upregulation of antiphagocytic genes IL-10, CD16, IL-18 and MMP-9. Some core canonical pathways showing physiology of cellular signaling obtained by data analyzed by the Ingenuity software is confirmed a very complex mechanism still to be deciphered involved in the biology of TAM formation by which the rogue cancer cells tame their enemies, the macrophages and actually make them their helper cells to survive and propagate in the tumor microenvironment and thus prepare for epithelial mesenchymal transition for future metastasis and cancer stem cell formation and progression.
A 65 year old gentleman was referred with symptoms of haematuria and haematospermia in association with an elevated prostate specific antigen (PSA). He was investigated with a flexible cystoscopy, Ultrasound scan and a computed tomography (CT) of his abdomen and pelvis. These failed to reveal any abnormality. Magnetic resonance imaging (MRI) revealed a Prostate Imaging Reporting and Data System PIRADS 2 lesion in the left peripheral gland and PIRADS 3 lesion on the right side posterolaterally at the level of mid gland of the prostate. He went on to have Transrectal ultrasound biopsies of his prostate (TRUS Bx) that excluded any pathology. On follow up visits his PSA continued to rise and he underwent Template biopsies of the prostate. The histological features had no evidence of any Prostatic intraepithelial carcinoma (PIN) or other malignancies. Flexible cystoscopy was repeated due to his persistent haematospermia. This showed prominent papillary lesions over his verumontanum and prostatic urethra. Biopsies from these areas revealed Ductal Adenocarcinoma of the Prostate (DACP). A subsequent staging MRI revealed unchanged appearance of the PIRADS2 nodule. There was however some low signal extending into the right seminal vesicle which is more pronounced than on the previous scan reported as PIRADS3. Subsequent mapping Template biopsies and Transurethral biopsies revealed a Gleason 4+4 DCAP. A staging CT and bone scan excluded any metastasis. He went on to receive an open radical prostatectomy and pelvic lymph node dissection as a curative treatment for his locally advanced disease.
Papillary thyroid carcinoma (PTC) has two major types, classic (PTCC) and follicular variant (FVPTC), which correlate with molecular findings and have varying clinical implications. We assessed the cytologic findings and subsequent surgical pathology findings with the molecular mutations in these two groups, including microcarcinomas. Fourty-four patients with PTC resections over a one-year period were retrospectively examined in conjunction with previous cytologic diagnoses. BRAF, NRAS and TERT promoter mutations for the resected specimens were analyzed. Correlation with previous cytology in regard to molecular mutations and tumor size (microcarcinoma) were made. Significantly more BRAF V600E mutations were seen with PTCC, whereas significantly more NRAS mutations were seen with FVPTC. TERT mutations were only seen with PTCC. Molecular studies for thyroid carcninomas are becoming increasingly more common and influence treatment and patient prognosis. BRAF and or TERT mutations are associated with a worse prognosis. NRAS mutations associated with FVPTC and may lead to milder cytologic changes compared to the BRAF- and TERT-driven PTCC.
Background: Expression of PD-L1 detected by immunohistochemistry can represent a new hope for cancer management. The role of PD L1 in breast cancer is still unclear. Similarly, is the role of tumor-infiltrating FOXP3 +ve regulatory T (Treg) cells where literature data are conflicting. Our study aimed to evaluate the immunohistochemical expression of PD L1 and FOXP3 in breast cancer, correlate them with clinicopathological parameters as well as evaluating their relation.
Methods: This is a retrospective study carried out on 136 breast cancer specimens. Only cases with proved pathological diagnosis of infiltrating duct carcinoma of no special type (NST) were included. Tissue microarray blocks were constructed and immunostained with the polyclonal antibody for PDL1 and monoclonal antibody for FOXP3.
Results: Statistically significant correlation was found between high FOXP3 and nearly all adverse prognostic factors including; grade III tumors (p =.003), basal-like subtype(p =.001), high Ki67(p =.001), negative ER status(p =.001), negative PR(p =.028), HER2 expression(p =.04), advanced stage (p =.001), and LN metastases(p =.001). For PDL1, only statistically significant correlation with high Ki67 (p =.018) and advanced stage(p =.03) was found. A statistically significant positive correlation was found between PD L1 and FOXP3(p=.001). No statistically significant correlation was found between both PDL1 and FOXP3 in relation to disease-free survival (DFS) (p =.054). PDL1, age (≥ 50 years), nodal metastases were significant predictors of relapse in breast cancer.
Conclusion: The current study supports PDL1 as a predictor of relapse in breast cancer. Additionally, it highlights the synergistic role between PDL1 and FOXP3 in breast cancer microenvironment. Each can be considered as a poor prognostic marker in breast cancer. This raises a concern about the benefit of breast cancer patients from blocking of PDL1 pathway.