The prevalence and clinical significance of HER2 expression in prostate adenocarcinoma.

AIMS: Abnormalities in HER2 are well-established oncogenic drivers and are approved therapeutic targets in various malignancies. Prior studies evaluating HER2 expression in prostate cancer (PCa) have yielded variable results. Most of these studies used immunohistochemistry scoring systems based on breast cancer data. The goal of this study was to determine the prevalence and clinical significance of HER2 expression using a scoring system that better reflects the HER2 staining pattern observed in PCa. METHODS: We randomly selected similar numbers of localized low risk (AJCC stage I), locally advanced (AJCC stages II & III), and metastatic (AJCC stage IV) PCa patients treated at the DC VA Medical Center between 2000 and 2022. Among them, we included patients who had sufficient PCa tissue samples and clinical information required for this analysis. Two experienced pathologists independently scored HER2 expression (Ventana Pathway anti-HER2) according to a modified gastric cancer HER2 scoring system. RESULTS: Out of the 231 patients included, 85 % self-identified as Black. 58.9 % of patients expressed HER2 (1+: 35.5 %; 2+: 18.2 %; 3+: 5.2 %). Validity of the results was confirmed using the HercepTest antibody. Higher HER2 expression was associated with a higher Gleason Score/Grade Group and advanced disease. CONCLUSIONS: Our findings support the adverse prognostic impact on HER2 in PCa. We propose the use of a modified scoring system to evaluate HER2 expression in PCa. The observed high prevalence of HER2 expression supports the consideration of novel HER2-targeted therapies addressing even low levels of HER2 expression in future PCa trials.

Ductal Adenocarcinoma of the Prostate with Novel Genetic Alterations Characterized by Next-Generation Sequencing.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).

Secretomes from Conventional Insemination and Intra-Cytoplasmic Sperm Injection Derived Embryos Differentially Modulate Endometrial Cells In Vitro.

Conventional Insemination (CI) and Intra-Cytoplasmic Sperm Injection (ICSI) are routinely used insemination methods in clinical Assisted Reproductive Technologies (ART) settings. However, the existing data on the developmental competence and implantation potential of CI and ICSI derived embryos are not unequivocal. This prospective study on 23 patients undergoing ART treatment explored whether the secretomes of CI- and ICSI-derived embryo differentially alter the expression of integrins (αv and ß3 integrin) and MUCIN-1 (MUC-1) in a human endometrial epithelial cell line (Ishikawa). Immunocytochemical data demonstrated that the secretome of CI-derived top quality (GI) embryos induced higher (p < 0.05) expression of ɑv ß3 compared to sibling ICSI derived G1 embryos in Ishikawa cells. Though, relative levels of the transcript for MUC-1, anti-adhesion molecule did not show a significant difference between the study groups, immunocytochemical analysis demonstrated significantly (p < 0.0001) higher expression of MUC-1 in cells treated with ICSI-derived embryo secretome, compared to that treated with CI -derived embryo secretome. These results suggest that secretomes from CI and ICSI embryos differentially modulate the endometrial cells in vitro. This hints at differences in the ability of CI- and ICSI- derived embryos to alter endometrial profile.

Expression of Marker PAK1 in Sinonasal Polyposis.

Introduction Chronic rhinosinusitis with nasal polyposis involves mucosal lining of nose and paranasal sinuses. Numerous studies studied the mechanism leading to sinonasal polyposis. We attempted study the inflammatory mechanisms responsible for the recruitment and activation of leukocytes. Aim To study and compare the expression of the immunohistochemistry marker PAK1 in sinonasal polyposis and normal nasal mucosa. Material and Methods Prospective observational study done by comparing two groups of 30 each with Group A comprises Sinonasal polyposis and Group B comprises normal nasal mucosa. The specimens were subjected to PAK1 immunohistochemical staining. Results Immunihistrochemical staining showed higher intensity stain in sinonasal polyp when compared to normal nasal mucosa. Conclusion The upregulation of PAK1 in sinonasal polyposis when compared to normal nasal mucosa may indicate an increased cellular proliferation and turnover in the background of chronic inflammation.

Prognostic significance of receptor for hyaluronan acid-mediated motility (CD168) in acute pediatric leukemias - assessment of clinical outcome, post induction, end of treatment and minimal residual disease.

INTRODUCTION: The extracellular matrix protein hyaluronan acid plays an active in role in tumor cell proliferation and invasion. Hyaluronan acid receptors, namely CD168 or the receptor for hyaluronan acid-mediated motility (RHAMM) and CD44 have been implicated in promoting malignancy. There is a lacuna in data on the expression of the receptor in pediatric leukemias. METHODS: Pediatric patients with acute leukemia who were diagnosed, treated and followed up in our center were enrolled. The bone marrow biopsies performed prior to treatment were subjected to immunohistochemical staining (54 biopsies: acute lymphoblastic leukemia - 45, acute myeloid leukemia - 9). Blast counts were carried out at diagnosis, end of the induction phase and end of chemotherapy, the minimal residual disease was assessed and follow up details were collected. Positivity was correlated with initial blast count, post-induction blast count, minimal residual disease and patient survival. RESULTS: There was no correlation between the initial blast count and the percentage of blasts with RHAMM expression. The positive correlation between percentage of blasts expressing RHAMM and the post-induction blast count was moderate in acute myeloid leukemia (0.74) and mild in acute lymphoblastic leukemia (0.48). There was a statistically significant difference in RHAMM expression between the two minimal residual disease risk groups (p-value = 0.012) with a negative prognostic effect of RHAMM expression. Moreover, a negative prognostic effect of RHAMM expression was noted when patient survival was considered. CONCLUSION: This study shows that blasts in acute myeloid leukemia show more RHAMM positivity than those of acute lymphoblastic leukemia indicating the aggressive nature of this type of leukemia. In acute leukemias, patients with high percentages of RHAMM-positive blasts had more post-induction blasts, blasts in minimal residual disease and poorer prognosis.

Paediatric Peripheral Primitive Neuroectodermal Tumour - A Clinico-Pathological Study from Southern India.

INTRODUCTION: Primitive Neuroectodermal Tumour (PNET)/Ewing Sarcomas (ES) are aggressive childhood malignancies with neuroectodermal differentiation. AIM: To study the clinical presentation, morphology, Immun-ohistochemistry (IHC), management and outcome of all the cases of paediatric pPNET/ES reported in our tertiary care centre over a period of six years. MATERIALS AND METHODS: This was a retrospective study conducted at Sri Ramachandra Medical College and Research Institute, Chennai, India. All biopsy proven cases of peripheral PNET/ES, in patients less than 18 years of age for a period of six years were included in this study. The corresponding clinical details regarding initial presentation, treatment and follow up were retrieved from the case files and analysed. Survival rate was calculated and Kaplan-Meier survival curve was plotted. RESULTS: We describe eleven cases of paediatric peripheral PNET/ES. The mean age at presentation was 94.08 (±58.27) months with a male/female ratio of 1.2:1. About 27.3% cases, all male with a mean age of 140 months at presentation, had distant metastasis during initial diagnosis. Biopsy showed small round blue cell morphology on light microscopy. IHC revealed strong membranous staining for CD99 in all cases. All children were treated with neo-adjuvant chemotherapy and then surgery, followed by radiotherapy if indicated. The cases were followed up for a mean duration of 20.82 months (ranging from one to 66 months). Nine children are doing well on follow up (81.8% survival rate). Two cases with metastasis at initial presentation died. Patients with metastatic disease exhibited a mean duration of survival of 9.66 (±7.24) months and those with localized disease exhibited a mean duration of survival of 25 (±22.88) months. CONCLUSION: Metastasis at diagnosis is the single most important factor affecting prognosis. This was reflected in the present study where cases with metastasis exhibited a short mean duration of survival when compared to localized disease. It is likely that many cases of PNET/ES were not accurately identified in the past as IHC plays a vital role in the diagnosis of these small round blue cell tumours. IHC in adjunct with molecular studies has improved diagnostic accuracy. Multidisciplinary management and good supportive care when the lesion is localized has lead to improved survival.

Co-Incidence or Co-Existence? Acute Lymphoblastic Leukaemia in HbE-alpha Thalassaemia: A Case Report with Review of Literature.

Haemoglobin E (HbE) is a Haemoglobin variant that commonly occurs in many places in Asia. As ß thalassaemia and α thalassaemia also occur in the same regions, the co-inheritance of these conditions leads to various phenotypic forms. HbE α thalassaemia is less common and of a milder phenotype than HbE ß thalassaemia. Though malignancies are one of the complications in thalassaemia, occurrence of leukaemia is a rare event. Here we present a case of a two-year-old male child co-presenting with pre B acute lymphoblastic leukaemia (ALL) with MLL rearrangement and HbE alpha thalassaemia. The child is on remission 12 months post-therapy with standard ALL high risk protocol with no minimal residual disease (MRD). Haematological and oncological conditions coexisting at presentation is a challenge to therapy. This case is described for its rarity. Informed consent has been obtained from the parents.

Biological Reference Interval for Hematological Profile of Umbilical Cord Blood: A Study Conducted at A Tertiary Care Centre in South India.

INTRODUCTION: Umbilical cord blood (UCB) a source of hematopoietic stem cells, is also an acceptable sample to assess neonatal sepsis. Though reports are available for stem cell counts very minimal literature is available regarding hematologic parameters, which may vary on ethnicity. AIM: To establish biological reference interval for hematological parameters of umbilical cord blood to guide neonatologists, hematopoietic stem cell transplant specialists and future analysis. MATERIALS AND METHODS: Prospective longitudinal study was done from January 2014 to April 2014 after ethics committee approval. UCB from 120 full term new borns of normal birth weight born out of uneventful pregnancy to mothers aged between 21 to 45 years with hemoglobin above 10g/dL were processed in Beckman Coulter LH780 analyzer for complete blood count and counter checked by peripheral smear. Results tabulated in Microsoft excel are analyzed using IBM SPSS statistics 16 software. RESULTS: Male to female ratio is 1:1.05. There is no difference in the values between males and females. When compared with few studies available, though many values are comparable a few values are not comparable. CONCLUSION: This study can be a useful guide to neonatologists, hematopoietic stem cells transplant hematologists and future analysis.

Prognostic significance of receptor for hyaluronan acid-mediated motility (CD168) in acute pediatric leukemias - assessment of clinical outcome, post induction, end of treatment and minimal residual disease

ABSTRACT Introduction: The extracellular matrix protein hyaluronan acid plays an active in role in tumor cell proliferation and invasion. Hyaluronan acid receptors, namely CD168 or the receptor for hyaluronan acid-mediated motility (RHAMM) and CD44 have been implicated in promoting malignancy. There is a lacuna in data on the expression of the receptor in pediatric leukemias. Methods: Pediatric patients with acute leukemia who were diagnosed, treated and followed up in our center were enrolled. The bone marrow biopsies performed prior to treatment were subjected to immunohistochemical staining (54 biopsies: acute lymphoblastic leukemia - 45, acute myeloid leukemia - 9). Blast counts were carried out at diagnosis, end of the induction phase and end of chemotherapy, the minimal residual disease was assessed and follow up details were collected. Positivity was correlated with initial blast count, post-induction blast count, minimal residual disease and patient survival. Results: There was no correlation between the initial blast count and the percentage of blasts with RHAMM expression. The positive correlation between percentage of blasts expressing RHAMM and the post-induction blast count was moderate in acute myeloid leukemia (0.74) and mild in acute lymphoblastic leukemia (0.48). There was a statistically significant difference in RHAMM expression between the two minimal residual disease risk groups (p-value = 0.012) with a negative prognostic effect of RHAMM expression. Moreover, a negative prognostic effect of RHAMM expression was noted when patient survival was considered. Conclusion: This study shows that blasts in acute myeloid leukemia show more RHAMM positivity than those of acute lymphoblastic leukemia indicating the aggressive nature of this type of leukemia. In acute leukemias, patients with high percentages of RHAMM-positive blasts had more post-induction blasts, blasts in minimal residual disease and poorer prognosis.