Clinicopathological parameters associated with cervical lymph node metastases in differentiated thyroid cancer.

BACKGROUND:  Lymph node metastasis (LNM) has an important role for the prognosis of diferentiated thyroid cancer (DTC). The aim of the study was to investigate the efect of clinicopathologic parameters on cervical LNM in DTC. METHODS:  The patients who underwent thyroidectomy along with neck dissection were analyzed retrospectively. RESULTS:  Of the 150 patients diagnosed with DTC who underwent neck dissection, 1 had follicular thyroid carcinoma and 149 had papillary thyroid carcinoma (PTC). The median tumor size was 14.0 mm. The tumor diameter with the highest specificity and sensitivity for the detection of LNM was >11.5 mm. Extrathyroidal extension (ETE) was observed in 35.3% of the patients. The rate of multifocality in tumors with extrathyroidal spread was significantly higher than in tumors without ETE. LNM was observed in 60.0% of the patients. ETE was present in 28.9% of the tumors that had LNM. Lymphovascular invasion (LVI), perineural invasion (PNI), and positive surgical margin were observed in 13.3%, 2.7%, and 14% of the patients respectively. A significant positive correlation was found between LNM and tumor diameter, ETE, positive tumor margin and LVI (Pp=.006, P=.031, P = .002, and P=.014, respectively). CONCLUSION:  In this study, ETE, LVI, positive tumor margin, and tumor diameter greater than 11.5 mm were significantly correlated with the presence of LNM. These findings may be useful in bringing to mind the possibility of lymph node metastases that have not been able to be detected before surgery and in monitoring these patients more closely.

Timing of the repeat thyroid fine-needle aspiration biopsy: does early repeat biopsy change the rate of nondiagnostic or atypia of undetermined significance cytology result?

PURPOSE: To determine whether early repeat fine needle aspiration biopsy (FNA) has an effect on adequate or atypia of undetermined significance (AUS) cytology rates in thyroid nodules with inadequate or AUS result in the first FNA. METHODS: Nodules of patients who underwent repeat biopsy due to insufficient or AUS cytology between 2019-2022 were included. Data of the patients and ultrasonographic, cytological and histopathological results of the nodules were recorded. Additionally, the time between the two biopsies was noted. The first was called "initial" and the second was called "rebiopsy". Five different paired groups were formed according to the time between two consecutive biopsies; before and after 1 month, 45 days, 2 months, 3 months, and 6 months. The groups were compared in terms of adequate and AUS cytological results. RESULTS: We evaluated 1129 patients with 2187 nodules undergoing FNAB. After excluding nodules with one FNA result and/or missing data, 966 nodules of 628 patients who underwent FNA at least twice were included. Initial cytology was nondiagnostic (ND) in 665 (30.4%) and AUS in 301 (13.8%) nodules. The mean age of the patients was 52.0 ± 11.9 years, and the female sex ratio was 78.8% (n = 495). There were no differences in adequate or AUS rebiopsy results according to the different time interval groups (p > 0.05 for all). AUS result was statistically insignificantly more frequent in nodules with initially AUS nodules when rebiopsy was performed before 1 month in comparison to after 1 month (53.8%, 27.1%; p = 0.054). Accuracy of rebiopsy was also similar in the time intervals groups (p > 0.05 for all). CONCLUSION: In patients with inadequate or AUS initial biopsy, the rate of adequate or AUS cytology results at rebiopsy did not vary with the timing of repeat biopsy indicating that there may be no need to wait 1 month for a repeat biopsy. In patients with suspicious nodules, biopsy might be repeated before 1 month.

Should we rely on frozen section during the reimplantation stage of revision knee arthroplasty?

OBJECTIVE: To compare Frozen Section (FS) results during the reimplantation stage of revision knee arthroplasty, in patients without clinical signs of infection but with preoperative inconclusive serum inflammatory markers. METHODS: Sections were revisited the day after surgery. Intraoperative FS (iFS) was accepted as positive when the presence of >5 polymorphonuclear neutrophils (PMNLs) in 5 separate high-power fields was determined according to the consensus criteria of the International Consensus on Musculoskeletal Infection. The clinical outcomes, cultures and diagnostic values of iFS and review FS (rFS) were analyzed. RESULTS: No complications developed after reimplantation in 66 (84.6%) of the 78 evaluated patients. Complications developed in 12 patients, six of whom were treated with re-explantation, four with arthrodesis and two with above-the-knee amputation. Both iFS and rFS yielded insignificant sensitivity and specificity (25% and 45.5%, 25% and 45%, respectively). There was no statistically significant difference between definitive culture and iFS and rFS. CONCLUSION: iFS evaluation is insufficient to exclude recovery from periprosthetic joint infection (PJI). Diagnosis of recurrence of infection in patients with indefinite serum inflammatory markers between the explantation and reimplantation interval remains challenging due to massive fibrosis that makes proper tissue sampling difficult. The attending physician should closely monitor clinical findings.

How Can We Diagnose Ocular Surface Squamous Neoplasia With Optical Coherence Tomography?

AIM: We aimed to evaluate the effectiveness of optical coherence tomography (OCT) in the differential diagnosis of anterior segment diseases such as ocular surface squamous neoplasia (OSSN) and pterygium. METHODS: Patients who were pre-diagnosed with either OSSN (21) or pterygium (19) between January 2020 and November 2022 were included in this retrospective study. Anterior segment photographs and anterior segment optical coherence tomography (AS-OCT) measurements were obtained from each patient. Excisional or incisional biopsy materials underwent pathological evaluation. RESULTS: Preoperative AS-OCT images of the patients with OSSN showed similarities with histopathological specimens. Both ocular and pathological specimens appeared to have a thicker epithelial layer with a distinct change from healthy to neoplastic epithelium. Preoperative AS-OCT images of individuals with pterygium were also comparable with histopathological samples. Both pathological and AS-OCT images of the pterygium patients showed a normal thickness epithelium and a thickened subepithelial layer under the epithelium. The mean epithelial thickness measured with AS-OCT in OSSN patients was found to be 295.3 ± 111.3 µm, while it was 80.7 ± 43.4 µm in pterygium patients. The difference was statistically significant (P<0.001). The receiver operating characteristic (ROC) curve analysis revealed a cut-off value of 97 µm for the differential diagnosis of OSSN from pterygium, with a sensitivity of 100% and specificity of 94.7%. CONCLUSIONS: AS-OCT can be used as a noninvasive diagnostic tool for the evaluation of ocular surface lesions. Its ability to distinguish between OSSN and pterygium is demonstrated by the statistically significant difference in epithelial thickness and the significant morphological association with histopathological findings.

Ultrasonographical, clinical and histopathological features of 1264 nodules with papillary thyroid carcinoma and microcarcinoma based on tumor size.

OBJECTIVE: We aimed to evaluate the patients diagnosed with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) in terms of clinical, ultrasonographical (US) and histopathological features and their relationships with tumor size. METHODS: We retrospectively evaluated 881 patients who underwent thyroid surgery in our clinic and diagnosed with PTC histopathologically were enrolled the study. Demographic characteristics, US findings and histopathological features were evaluated. RESULTS: In total, 1264 nodules were identified in the 881 patients. The incidentality rates were higher in the PTMC group and also in the ≤ 5 mm group. In total multifocality rate was 32.9%, and was significantly higher in PTMC group than the PTC group. PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, were more aggresive histopathological features. CONCLUSION: Since the incidentality rates were found significantly more common in our patients with PTMC and those with ≤ 5 mm, ultrasonographic features of the nodules should be evaluated carefully and for cases which are suspicious with US, US-guided fine needle aspiration biopsy (FNAB) should be considered in order to make the correct treatment strategy. Also our study revealed that PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, have more aggresive histopathological features.

Evaluation of corneal topography, tear film function and conjunctival impression cytology after long-term scleral contact lens wear in keratoconus patients.

Purpose: To investigate the impact of long-term scleral contact lens (ScCL) wear on corneal curvature, corneal thickness, tear film function, and ocular surface in patients with keratoconus.Methods: Sixteen keratoconus patients wearing ScCLs for 6 months were enrolled in the study. Corneal topography, tear osmolarity test, Schirmer 1 test, tear film break-up time (TBUT) test, and impression cytology analysis were assessed at baseline and follow-up examinations.Results: There were no significant differences in visual acuity, keratometric and pachymetric values after 6 months of ScCL wear compared to baseline (p>0.05 for all). Tear osmolarity, Schirmer 1 test, and TBUT test results showed no significant change during follow-up (p>0.05 for all). Median goblet cell density and grade of squamous metaplasia did not differ significantly at 1-month. However, there was a gradual deterioration in goblet cell density and Nelson grade until the third-month visit compared to baseline (p for goblet cell, p=0.003; p for Nelson grade, p=0.003). These impaired cytological features observed at 3-month visit persisted at 6-month visit (p for goblet cell, p=0.008; p for Nelson grade, p<0.001).Conclusion: Six months of ScCL wear did not induce any changes in corneal curvature and thickness and also did not affect tear function tests in keratoconic eyes. The only significant changes observed were a decrease in goblet cell density and metaplastic changes in conjunctival epithelium in impression cytology analysis. Further investigations may be needed to better understand the cause of impairment in cytological features of ocular surface and its clinical implications.

Irisin Protects Against Hind Limb Ischemia Reperfusion Injury.

AIM: The aim of this study was to evaluate the effects of irisin in a murine model of hind limb ischemia reperfusion (I/R). METHODS: The mice were divided into four groups (n = 6 in each group): control, irisin, ischemia reperfusion (I/R), and irisin-ischemia reperfusion (I-I/R). Irisin (0.5 µg.g-1, intraperitoneally [i.p.]) was administered 30 min before the I/R procedure. After 2 h of ischemia and 2.5 h of reperfusion, blood and tissue samples were taken for biochemical and histopathological analysis. The results were analyzed by Kruskal-Wallis and Mann-Whitney U-tests. RESULTS: There was a statistically significant difference in the total antioxidant status (TAS) and total oxidant status (TOS) levels in all the groups. The TAS level in the I/R group was significantly lower than that in the control, irisin, and I-I/R groups, whereas the TOS level was significantly higher in the I/R group as compared with that in the other groups. Caspase-3 activity and caspase-8 activity, indicators of inflammation, were significantly higher in the I/R and I-I/R groups as compared with those in the control and irisin groups. CONCLUSION: Irisin may have protective effects in skeletal muscle ischemia reperfusion injury.

Ultrasonographical, clinical and histopathological features of 1264 nodules with papillary thyroid carcinoma and microcarcinoma based on tumor size

ABSTRACT Objective: We aimed to evaluate the patients diagnosed with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) in terms of clinical, ultrasonographical (US) and histopathological features and their relationships with tumor size. Subjects and methods: We retrospectively evaluated 881 patients who underwent thyroid surgery in our clinic and diagnosed with PTC histopathologically were enrolled the study. Demographic characteristics, US findings and histopathological features were evaluated. Results: In total, 1264 nodules were identified in the 881 patients. The incidentality rates were higher in the PTMC group and also in the ≤ 5 mm group. In total multifocality rate was 32.9%, and was significantly higher in PTMC group than the PTC group. PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, were more aggresive histopathological features. Conclusions: Since the incidentality rates were found significantly more common in our patients with PTMC and those with ≤ 5 mm, ultrasonographic features of the nodules should be evaluated carefully and for cases which are suspicious with US, US-guided fine needle aspiration biopsy (FNAB) should be considered in order to make the correct treatment strategy. Also our study revealed that PTC and > 5 mm PTMC groups compared to PTMC and ≤ 5 mm groups respectively, have more aggresive histopathological features.

The Triple Positivity for EBV, PD-1, and PD-L1 Identifies a Very High Risk Classical Hodgkin Lymphoma.

BACKGROUND: The programmed death receptor (PD-1) and ligand (PD-L1) pathway act by suppressing the antitumor response in chronic Hodgkin lymphoma (cHL). In this study, we aimed to investigate the effect of PD-1, PD-L1, and Epstein-Barr virus (EBV) positivity on prognosis at the initial diagnosis of cHL. MATERIAL AND METHODS: Thirty-six patients with cHL were retrospectively analyzed. PD-L1 staining was performed for RS cells and tumor microenvironment in the biopsy materials of cases. The presence of EBV was investigated by EBER (EBV-encoded RNA) method in tumor cell. P < .05 was accepted as significant. RESULTS: The presence of advanced-stage disease, B symptoms, intermediate or high-risk international prognostic index (IPS), and extranodal involvement were found to be related to both PD-L1 positivity and EBV positivity in RS cells. PD-L1 positivity in RS cells was also associated with EBV positivity. There were 6 (16.7%) triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) patients. All of these patients had advanced-stage disease, B symptoms at the time of diagnosis, and intermediate-high IPS score, and 4 of 6 patients had extranodal involvement. This group also had significantly shortened overall survival compared with others (38.4 months vs. 67.9 months P = .024). CONCLUSION: Our data suggest that there is correlation between PD-L1 positivity and EBV positivity in tumor RS cells that are also associated with extranodal involvement, intermediate and high IPS score, presence of B symptoms, and advanced-stage disease. In addition, we identified a group of triple-positive (EBV+, RS-PD-L1+, mic-PD-1+) cHL patients who have a very high-risk disease.

Tear function and ocular surface changes following corneal collagen cross-linking treatment in keratoconus patients: 18-month results.

PURPOSE: To investigate the long-term effects that CXL has on the tear function and ocular surface in keratoconus. METHODS: Twenty-one consecutive patients (24 eyes) with progressive keratoconus scheduled for CXL were included. All patients underwent the following procedures: conjunctival impression cytology analysis, ocular surface disease index (OSDI) score, tear osmolarity test, Schirmer test, tear film breakup time (TBUT), ophthalmic surface fluorescein (Fl) staining, and topographical corneal evaluation before as well as 3 and 18 months after accelerated CXL. RESULTS: There was no change in the median OSDI score, tear osmolarity test, Schirmer test, and the Fl staining score after CXL. The median TBUT increased from 9.00 s at baseline to 12.00 s at 18 months postoperative (P < 0.001). The cytological features of the temporal and superior bulbar conjunctiva deteriorated at 3 months post-CXL (P < 0.001). An improvement in impression cytology analysis of the temporal conjunctiva was noted at 18-month follow-up (P < 0.001). Significant improvements in the median maximum keratometry and mean keratometry (K-mean) readings were also noted 18 months after CXL (P < 0.001). The changes in the K-mean correlated significantly with the changes in TBUT levels at 18-month follow-up as compared to baseline (r = - 0.688, P < 0.001). CONCLUSIONS: The improvement in TBUT, conjunctival squamous metaplasia, and the goblet cell density indicates a favorable effect of CXL on the ocular surface and tear film in keratoconus, presumably due to the reduced corneal irregularity after CXL.

Are cytologic and histopathologic features of hot thyroid nodules different from cold thyroid nodules?

BACKGROUND: We aimed to compare the cytology and histopathology results of hot, cold, and warm nodules in patients who had thyroidectomy due to toxic multinodular goiter (TMNG). METHODS: Five hundred and nine thyroid nodules from 413 patients who had operation with TMNG were included in this retrospective study. The nodules were categorized as hot, cold, and warm groups. The cytology and histopathology results were compared. RESULTS: The 509 thyroid nodules were grouped as hot (n = 364 [71.5%]), cold (n = 122 [24.0%]), and warm (n = 23 [4.5%]) according to scintigraphy. Cytological evaluations of 364 hot nodules were as follows: 80 (22%) nondiagnostic (ND), 259 (71.2%) benign, 17 (3.6%) atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS), 2 (0.5%) follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 2 (0.5%) suspicious for malignancy (SM), and 4 (1.1%) malignant. The cytology of 122 cold nodules were ND in 25 (20.5%), benign in 86 (70.5%), AUS/FLUS in 8 (6.6%), FN/SFN in 1 (0.8%), and finally SM in 2 (1.6%). The 23 warm nodules were determined as ND, benign, and FN/SFN in 7 (30.4%), 15 (65.2%) and 1 (4.3%), respectively. There were no differences according to cytological results between groups (P = .616). However, malignancy rate was 3.8% in hot nodules, it was found as 6.6% in cold nodules. The malignancy was detected in 4.3% of warm nodules. There were no differences in malignancy rates between groups (P = .459). CONCLUSION: We demonstrated similar malignancy rates in hot nodules when compared with cold and warm nodules.

A cancer of undetermined significance: Incidental thyroid carcinoma.

INTRODUCTION: The incidence of thyroid cancer is increasing which can be attributed in part to improved ultrasonography (US) methods and increased detection of incidental thyroid carcinomas (ITC). We aimed to compare ITC with nonincidental thyroid carcinomas (NITC) in this study. METHODS: Retrospective analyses of 906 individual patients who were operated for benign and malignant thyroid disease and had a final histopathological diagnosis of thyroid carcinoma were enrolled in this study. Preoperative US examination and fine needle aspiration (FNA) biopsy results were evaluated. The tumor foci in thyroidectomy specimens that were not represented in preoperative US or FNA reports were classified as ITC. The tumor foci that match with the lesions defined in US or FNA results were classified as NITC. RESULTS: Final histology revealed ITC in 326 patients (36%) and NITC in 580 patients (64% Mean age was 51.7 ± 11.11 in ITC group and 48.15 ± 13.1 in NITC group (P < .001). In NITC group 322 (55.5%) of the patients were operated for suspicious cytology while only 29 (8.9%) of the patients in the ITC group were operated because of this indication (P < .001). There were 1301 cancer foci in histopathology specimens. Among all these cancer foci, 434 (33.3%) were detected incidentally and 867 (66.7%) were detected non-incidentally. About 779 (89.9%) of nonincidental cancer foci were papillary cancer (PTC), while all of the incidental cancer foci were PTC. Mean size was 13 mm in NITC group and it was 3 mm in the ITC group and differed significantly between the groups (P < .001). Tumor size was ≤1 cm in 35.2% of the patients with NITC while 98.5% of patients with ITC had tumor ≤1 cm. The occurrence of multinodularity was higher in ITC than the NITC group (P < 001). Median TSH level was higher in patients with NITC than ITC while both were in the reference range (1.53 vs 1.03 µIU/mL, P < .001). The frequency of thyroiditis detected by US, and thyroid peroxidase antibody and thyroglobulin antibody positivities were similar in patients with ITC and NITC (P = .2, P = .86, and P = .26, respectively). The frequencies of capsular invasion (29.1% vs 7.9%), extrathyroidal extension (13% vs 4.2%), multifocality (35.8% vs 24.2%), non-complete resection (9.2% vs 1.8%), and lymph node metastasis (9.5% vs 1.8%) were significantly higher in the NITC group (P < .001, for each). Persistent/recurrent disease in patients with NITC was more frequent than patients with ITC (P = .004). This outcome was similar for cancers measuring ≤1 cm (P = .001). CONCLUSION: ITC is often encountered in older patients and frequently determined in early stages with more favorable histopathological features and better prognosis.

Expression of Immunomodulatory Molecules PD-1, PD-L1, and PD-L2, and their Relationship With Clinicopathologic Characteristics in Endometrial Cancer.

Chemotherapeutic agents are not very effective in treating advanced endometrial cancers (ECs). Recent studies have demonstrated the immune evasion mechanism of tumors and possible remedies. Programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and programmed death ligand 2 (PD-L2) are immunomodulator molecules that have been the focus of research in lung cancer, melanoma, and renal cell cancer. However, there are few studies concerning EC. This retrospective study aimed to determine PD-1, PD-L1, and PD-L2 expression immunohistochemically in EC, and to study their correlation with clinicopathologic tumor characteristics. This study comprised 127 patients with EC. Anti PD-1, PD-L1, and PD-L2 antibodies were examined immunohistochemically on sections obtained from tissue microarray paraffin blocks. No staining with PD-1 in tumor cells was seen; however, we found positive staining in tumor cells at 36.2% with PD-L1 and 64.4% with PD-L2, and at 61.6% with PD-1, 36.2% with PD-L1, and 93.2% with PD-L2 in immune cells. When comparing staining and clinicopathologic findings, most of the PD-L1 negative tumors (both in tumor and immune cells) were FIGO Stage I, which was significantly higher than stage II-III-IV tumors (P<0.05). There was a statistically significant association between the FIGO grade and the PD-L1 score in immune cells (P=0.009), and between staining of PD-1, PD-L1, and PD-L2 and age (P=0.004, 0.013, and 0.043, respectively). Interaction between PD-1, PD-L1, and PD-L2 may be a potential target for immunotherapy in elderly and advanced stage EC patients.

Exenatide reduces oxidative stress and cell death in testis in iron overload rat model.

Glucagon-like peptide-1 (GLP-1) has been demonstrated to affect the oxidative stress status in several in vitro, in vivo and clinical studies. The aim of the present study was to evaluate the effect of a GLP-1 analogue, exenatide, on oxidative stress parameters and apoptotic markers in testicular cells in an iron overload rat model. To obtain this model, the animals were randomly divided into three groups (n=6/group). Rats in the control group received intraperitoneal injections of saline. Intraperitoneal iron dextran (60 mg/kg/day) was given to Group FE for 5 days a week for 4 weeks. The third group (Group Fe +E) was given subcutaneous injections of 10 µg/kg exenatide in two divided doses for 4 weeks in addition to iron dextran. Testes of all rats were immediately removed for immunohistochemical staining and to measure the malondialdehyde level and superoxide dismutase enzyme activity. A significant reduction was observed in caspase-8 and -3 enzyme staining in testicular stromal and endothelial cells in exenatide injected iron overloaded rats when compared with controls. Oxidative stress markers malondialdehyde levels and superoxide dismutase enzyme activities were also significantly lower in exenatide-injected rats when compared with controls. These findings indicate that exenatide may be protective against the harmful effects of iron accumulation in testis. Further studies are required to evaluate how exenatide reduces oxidative stress and cell death in iron overloaded testis tissue.

Effects of hydroxyethyl starch 130/0.4 on the kidney tissue of rats with ureteral obstruction.

OBJECTIVE: This study was conducted since the effects of colloid solutions on the renal system remain controversial and need to be adequately studied in animals. We aimed to evaluate the effects of hydroxyethyl starch (Voluven) on the kidney tissue of rats with late renal failure due to ureteral obstruction. MATERIALS AND METHODS: Rats were divided into four groups: Group C, control; Group HES, hydroxyethyl starch solution (HES) 130/0.4 (Voluven®); Group UUO, unilateral ureteral obstruction (UUO); and Group UUO-HES, UUO-HES 130/0.4 (Voluven®). In the groups with ureteral obstruction, the distal part of the right ureter was accessed and sutured through a lower abdominal incision under ketamine anesthesia. Any signs of late-stage renal failure were evaluated after three weeks. Rats in the HES group and the renal failure-HES group were administered with HES 130/0.4 as a single intravenous dose of 20 mL/kg. After a follow-up of 24 hours, intra-abdominal blood sample was collected, and the rats were sacrificed. Biochemical and histopathological parameters were then evaluated. RESULTS: Ureteral obstruction significantly increased urea and creatinine levels. In addition, when the UUO-HES and HES groups were compared, the administration of HES increased urea and creatinine levels in the UUO-HES group. Nitric oxide enzyme activity and malondialdehyde levels have significantly increased in the UUO groups. In addition, HES significantly increased nitric oxide activity and malondialdehyde levels in the UUO-HES group, in comparison with the HES group. The activity of caspases 3 and 8 was significantly increased in the UUO groups. In addition, HES significantly increased the activity of caspases 3 and 8 in the UUO-HES group, in comparison with the HES group. Light microscopy revealed significant changes in the UUO groups, especially in the obstructed kidneys. CONCLUSION: If indicated, HES should be used with caution in cases of UUO, but not in the cases of bilateral ureteral obstruction. Other aspects of these findings, including the clinical significance and practical applications, merit further experimental and clinical investigation.

Association between Her2/neu status in colorectal carcinoma and clinicopathological features: a retrospective study using whole - tissue sections.

The human epidermal growth factor receptor 2 (Her2/neu) signal pathway plays a significant role in the occurance of various solid tumor types. The rate of Her2/neu in colorectal carcinoma (CRC) is not clearly elucidated. In this study, we discuss the association between Her2/neu overexpression and clinicopathological parameters in CRC. Her2/neu immunohistochemical (IHC) staining was performed on whole sections of formalin fixed paraffin embedded tumor tissues of 100 CRC resections. Cases with score 3+ and score 2+ expressions were further evaluated by silver in-situ hybridization (ISH) for the existence of Her2/neu gene amplification. Her2/neu membranous overexpression was observed in 12 of the 100 cases (6 cases with a score 3+ and 6 cases with a score 2+) and 6 of these were heterogenous. There were 10 cases with Her2/neu amplification (6/6 score 3+, 4/6 score 2+). Strong cytoplasmic staining was observed in 5 cases. Membranous scores were either 3+ or 2+ in 3 of these 5 cases. Moreover, there was Her2/neu amplification in 2 of these 3 cases. Her2/neu amplification status and overexpression was not related to clinicopathological parameters and overall survival. More clear results can be obtained from studies with Her2/neu IHC and ISH test on whole sections.

Prognostic significance of the programmed death ligand 1 expression in clear cell renal cell carcinoma and correlation with the tumor microenvironment and hypoxia-inducible factor expression.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common renal malignancy. Hypoxia-inducible factors, HIF-1α and HIF-2α, are expressed in the majority of ccRCC. Targeting immune checkpoints with the blockade of PD-1 and its ligand PD-L1 reorganizes T-cell activity in tumor microenvironment and provides important antitumor responses. PD-L1 upregulation has been found to be hypoxia-inducible factor (HIF) dependent. Our aim is to demonstrate the association between PD-L1 and HIF expression and to reveal the role of PD-L1 in prognosis and its association with tumor microenvironment. METHODS: Surgical specimens from 145 patients diagnosed with ccRCC, who had undergone radical or partial nephrectomy, were retrospectively analyzed. Immunohistochemistry on tissue microarrays (TMA) was performed to demonstrate expressions of PD-L1, HIF-1α, and HIF-2α in tumor cells and PD-1, CD4, and CD8 in lymphocytes to assess lymphocyte density in tumor microenvironment. RESULTS: PD-L1 tumor cell expression was detected in 20/125 (13.8%) cases, which correlated with higher levels of PD-1, CD4, CD8 and HIF-2α expression. Low or high expression of HIF-1α was similar in PD-L1-positive cases. When PD-L1-positive cases were compared with negative ones, there was no significant difference in terms of prognostic factors. However, the number of WHO/ISUP grade 3-4 tumors was significantly higher in PD-L1-positive cases than in negative ones. CONCLUSION: PD-L1 tumor cell expression is strongly associated with increased HIF-2α expression and presence of dense lymphocytic infiltration in ccRCCs. Our findings confirm that PD-L1 positivity is associated with high ISUP nucleolar grade. The association between PD-L1, HIF, and lymphocyte density in tumor microenvironment must be clarified and especially taken into account in combination treatment.

Evaluation of the Prognostic Importance of c-Myc and Bcl-2 Expressions and the Presence of Epstein-Barr Virus in Classical Hodgkin Lymphoma.

OBJECTIVE: Although classical Hodgkin lymphoma (cHL) has a relatively good prognosis, it also entails different treatment responses and involves patients who have different clinical courses. Our aim was to investigate c-Myc, Bcl-2 and EBV biomarkers in cHL and their relationship with the IPS score. MATERIAL AND METHOD: c-Myc and Bcl-2 immunohistochemical staining with EBER in situ hybridization (EBER-ISH) was applied to the paraffin sections of 94 cases diagnosed as cHL. These cases were classified into two groups as low and high clinical symptoms according to the International Prognostic Scores (IPS). RESULTS: Positive results were obtained in 83 (88.3%) cases with c-Myc and 39 (43.5%) cases with Bcl-2 while EBER-ISH was found positive in 42 (44.7%) cases. No difference was found between the groups of low/high IP scores with respect to the positive or negative results of EBER-ISH, Bcl-2 and c-Myc. When Bcl-2 and c-Myc positive cases were grouped together and compared to the IP scores of the remaining cHL cases, again no difference was seen. Extranodal involvement and bone marrow involvement was observed in 25 (26.5%) and 9 (9.5%) cases, respectively. Similarly, no statistically significant differences was found between these groups according to their positivity with EBER-ISH, Bcl-2 and c-Myc. CONCLUSION: We could not find any relationship between Bcl-2, c-Myc and EBER-ISH positivity and the low/high IPS groups in cHL. New studies with larger series are needed in which more precise cut-off values are used and clinically and biologically heterogeneous groups of cHL patients are determined more clearly.