Alev Ok Atilgan

Role of tumor-associated macrophages in the Hexim1 and TGFβ/SMAD pathway, and their influence on progression of prostatic adenocarcinoma

BACKGROUND Hexamethylene bisacetamide-inducible protein 1 (Hexim1) regulates transforming growth factor-β (TGFβ) activity and turnover of SMAD proteins in a cyclin-dependent kinase 9-dependent way. It does so specifically through inhibiting function of this enzyme and by inhibiting the transcriptional activity of positive transcription elongation factor b (P-TEFb). Tumor-associated macrophages (TAMs) play a role in the progression of prostate adenocarcinomas. We investigated the clinicopathological significance of Hexim1, TGFβ, SMAD2, and SMAD7 expression in prostate adenocarcinoma cells, and assessed associations between TAMs density and these proteins. METHODS The cases of 100 patients diagnosed with prostate acinar adenocarcinoma who had undergone radical prostatectomy were retrospectively examined. Each was reviewed for Gleason score, cancer stage, and specific histopathological features. Original slides were re-examined, and new slides were prepared and immunostained with Hexim1, TGFβ, SMAD2, SMAD7 and CD68. RESULTS Hexim1 expression was positively correlated with Gleason score, cancer stage, lymphovascular invasion, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Gleason score, cancer stage, perineural invasion, extracapsular extension, and positive surgical margin. TAMs density was positively correlated with Hexim1 expression and TGFβ expression. More advanced cancer stage, lymphovascular invasion, perineural invasion, and extracapsular extension were correlated with strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression, respectively. Strong Hexim1 expression, strong TGFβ expression, and mild SMAD7 expression were associated with higher Gleason score. Strong Hexim1 expression was correlated with strong TGFβ expression and mild SMAD7 expression. Strong Hexim1 expression, strong SMAD2 expression, and mild expression of SMAD7 were associated with disease progression. Strong SMAD2 expression was associated with shorter disease-free survival. CONCLUSION The results suggest that greater TAMs density, strong Hexim1 expression, strong SMAD2 expression, and mild SMAD7 expression play important roles in the progression of prostate adenocarcinoma. Further investigation of these proteins will help facilitate the definitive prognosis of prostate adenocarcinomas. Ultimately, these proteins may be therapeutic targets for patients with prostate cancer.

Peritoneal washing cytology in an adult granulosa cell tumor: A case report and review of literature

Adult-type granulosa cell tumors (AGCT) account for 1-2% of all ovarian tumors and 95% of granulosa cell tumors. In AGCT, at the time of peritoneal washing, tumor cells are rarely seen to exfoliate and FIGO stage is raised from IA/IB or IIA/IIB to stage IC or IIC despite the absence of a gross intraepithelial tumor. Patients with positive peritoneal washing cytology must be followed up for pelvic recurrence and metastasis. A more sensitive cytologic evaluation, histopathologic correlation and immunohistochemical staining can advance our practice. Here, we describe a case of AGCT with the emphasis on cytologic features observed in specimens obtained from peritoneal washing fluid.

Intraosseous angiolipoma of the frontal bone with a unique location: A clinical and pathological case illustration and review of the literature

Here, we report a case of a 16-year-old female patient was referred with scalp swelling and headache. Her neurological examination was normal and imaging of the skull revealed a well-defined lytic lesion measuring 15 mm × 6 mm to the right of the frontal bone. She was operated on with a prediagnosis of Langerhans cell histiocytosis. A wide excision with negative margins was made and the defect was reconstructed with a titanium plate. Subsequently, the lesion was histopathologically diagnosed as an angiolipoma of the frontal bone. The postoperative period was uneventful and she remained well during 1-year follow-up with no evidence of recurrence. Angiolipomas are rare benign lipomatous lesions located mostly in subcutaneous tissue of the forearm or trunk and frequently occur before puberty or in young adults. They are not common in bones. To the best of our knowledge, this is the first angiolipoma of the frontal bone reported.

Significance of Antibody-Mediated Vascular Rejection (AMVR) on Graft Survival: Correlation with Pure Antibody-Mediated Rejection (AMR)

Introduction Traditionally, endarteritis accepted to associate with cellular rejection. Nevertheless, some of the patients with AMR also had endarteritis at the same time. The risk of graft loss was nine times higher in AMVR than T cell-mediated rejection without endarteritis. However, the importance of the endarteritis on the graft survival in recipients with AMR is controversial. Thus we aimed to understand the prognostic value of the presence of endarteritis in recipients with AMR. Materials and Methods Among 155 recipients 72 (46,5%)had pure AMR (Group 1) while 83 (53,5%) had both AMR and endarteritis (Group 2). Endarteritis graded according to Banff. First indication biopsies of all cases reevaluated and the intensity of interstitial, glomerular and peritubular capillary (PTC) inflammation, neutrophil, macrophage and lymphocyte infiltration graded. HLA-DR expression in the arteries, PTCs, and tubules examined. The loss of DR expression on PTCs accepted as the destruction of PTCs. Follow-up biopsies analyzed for the development of interstitial fibrosis (IF), transplant glomerulopathy (TG) and transplant arteriopathy (TA). Results The extensity of the PTC and arterial C4d expression and the degree of PTC destruction found higher in Group 2 compared to Group 1 (P<.001).The degree of the interstitial eosinophil, plasma, and macrophage infiltration found higher in Group 2 patients than Group 1 (p<.001). Also, the intensity of inflammatory cells and neutrophils in both glomeruli and PTCs found higher in Group 2 compared to Group 1 (p<.001). Compared to Group 1 patients, Group 2 patients showed a higher incidence of IF, TG and TA in follow-up biopsies (p<.01).The development of IF and TG increases with the increasing degree of glomerulitis, PTC-itis, C4d expression and PTC destruction (p<.01). Also, the time of the development of IF and TG decreased with increasing intensity of PTC and interstitial infiltration, glomerulitis, PTC destruction and C4d expression (p<.01). The presence of the eosinophil and macrophage infiltration on the wall of arteries of recipients with AMVR rises the risk of the development of TG and TA (p<.01). Also, patients who had arterial C4d staining had a higher risk of TG, TA and graft loss (p<.001). The response to rejection therapy was lower in Group 2 recipients compared to Group 1 patients (p<.001). Overall the 3- and 5-year graft survival was 98%, and 85% respectively for Group 1 patients while it was 57%, and 27% respectively for Group 2 (p<.001). Conclusion Our results have underlined the importance of the presence of endarteritis in AMR. We showed that the course of AMVR are noticeably different from pure AMR, with AMVR having the worst outcome through leading the early development of IF, TG, and TA via augmenting inflammatory and fibrotic pathways. Thus the development of new treatment strategies for AMVR could salvage many kidney allografts.

Comparison of Recipients with Early and Later Presentation Polyomavirus Nephropathy (PVN) with Regard to Histological Findings and Graft Survival: What is the Influence of CD4/CD8 Ration on the Presenting Time of PVN

Introduction PVN is a common complication occurring around 12 months after transplant (Tx). Although unusual, the number of patients with late-presenting PVN is too much to underestimate. Thus, we aimed to understand if there are any differences between early and late-presenting PVN with regard to histological findings and graft survival. Materials and Methods All indication and follow-up biopsies of 71 patients with PVN re-evaluated and examined for the development of interstitial fibrosis (IF). Interstitial plasma cells, neutrophils, and CD3, CD4, CD8, HLA-DR positive cells, and macrophages graded. Patients separated into four groups in regards to the time of the development of PVN after Tx [Group A: <12 months (n:35), Group B: 12-24 months (n:13), Group C: 24-48 months (n:15), Group D: >48 months (n:8)]. Also, recipients correlated in two groups as Group 1 (n:48) early PVN (⩽12 months) and Group 2 (n: 23) late PVN (>12 months). Results The mean interval between the diagnosis of PVN and Tx was 17±22 months. Group 1 had higher mean hemodialysis (HD) time before Tx than Group 2 (p<.05). At the same time with PVN, CMV viremia was found in 27 patients. The mean viral load in urine and plasma at diagnosis was found higher in Group 1 than those Group 2 (p<0,01). Group 1 showed lower stages and higher degrees of polyoma viral load (Pvl) in biopsy compared to Group 2 (p<.05). Viral load in urine, plasma, and biopsy found to increase from Group A to Group D. Compared to Group 2; Group 1 showed higher degrees of interstitial neutrophil, plasma, macrophage, lymphocyte, DR-positive cell infiltration and lower degrees of the CD4/CD8 ratio (p<.01). All inflammatory cell types in interstitium found to increase from Group A to Group D. Interstitial CD4/CD8 ratio showed a significant negative correlation with Pvl (r=-0.320, p=.01), viremia (r=-0.602, p<.001) and viruria (r=-0.748, p<.001). Total 43 patients (60.6%) developed IF during follow-up, and 31 (43.7%) cases lost their graft at a mean time of 18±14 months after PVN. The risk of the development of IF increases from Group A to Group D (p<.01). Compared to Group 2 (28.7±16 months), the mean time of the graft loss after PVN was significantly early in Group 1 (13.3±9 months). The mean time of graft loss also decreases from group A to D (p<.05). Positive correlation found between the graft loss and CD4/CD8 ratio (r=0.391, p<.05). Conclusion This study pointed out that late-onset PVN is not uncommon. Recipients with late-onset PVN had a better prognosis than early-onset cases. Although the cause of late-onset PVN remains unclear, it is possible that host cells could influence the time of the onset of PVN. We showed that lower CD4 and higher CD8 proportions were risk factors for early-onset of PVN and poor graft survival. Contrarily patients who had high CD4/CD8 ratio developed late-onset PVN and better graft survival.

Effects of Adipose-Induced Stem Cell Application on Everolimus Immunosuppressed Rats on Colon Anastomosis: An Experimental Study

Background There are many factors that affect the safety of gastrointestinal anastomosis. In this study we aimed to investigate the effect of the stem cells that are derived from adipose tissue on wound healing in rats that are immune-suppressed with mTOR inhibitors Materials and Methods 56 rats were used and they were divided 4 groups: Group 1 (control, colonic anastomosis), group 2 (colonic anastomosis+stem cell), group 3 (colonic anasomosis+immunosuppression), and group 4 (colonic anastomosis+immune supression+stem cell). Adhesion, bursting pressure of the colonic anastomosis, tissue hydroxyproline level measurement, histopathologic and marked stem cell detection by florescent microscope examinations were done. Results Adhesion was most commonly seen in group 3 and stem cell application caused adhesions to be less visible in group 4. On the seventh day, higher tissue hydroxyproline levels were detected than in the fourth day (p<.001). Immunosuppression caused the tissue to decrease in hydroxyproline level. Stem cell administration caused an increase in the level of hydroxyproline in group 2 (p<.001), whereas group 4 did not cause the same effect. On the fourth and seventh day of anastomoses, the highest bursting pressure was found in group 2 and lowest in group 3. Although stem cell administration increased the bursting pressure in group 4 on the fourth day, the same effect was not seen on the seventh day. Histopathologic examination revealed a high level of vascular proliferation in the stem cell group (p<.001) Conclusions Subserosal stem cell injections to colonic anastomosis in immunosuppressed rats with everolimus increase the anastomotic resistance, and increase the vascular proliferation.

Human papilloma virus (HPV) negatif verrusiform ksantom: Skrotumda nadir görülen benign tümör

Verrusiform ksantom oldukca nadir gorulen ve genellikle oral mukozayi tutan benign bir neoplazidir. Mukoza disinda az sayida vaka ile vulva, skrotum, penis, anal bolge ve ekstremitelerde yerlestigi bildirilmistir. Makroskopik gorunumu nedeniyle klinik olarak kondiloma akuminatum, verrukoz karsinom ve skuamoz hucreli karsinom ile karisabilir. Ayirici tani icin mutlaka lezyonun eksizyonu ve histopatolojik incelemesi gereklidir. Bu lezyonun etyopatogenezi hala tartismalidir. Literaturde HPV enfeksiyonu pozitif vakalar bildirilmistir. Ancak HPV ile iliskisi net aciklanamamistir. Bu yazida, skrotumda yerlesim gosteren bir verrusiform ksantom olgusunu, nadir gorulmesi, HPV negatif olmasi ve klinik olarak malignite ile karismasi sebebiyle sunmayi amacladik.