Lowered IL-37 gene expression and elevated IL-37-producing tissue-resident immune cells in psoriasis lesional biopsies.

Psoriasis is an immune cell-dependent chronic autoimmune skin disorder. Interleukin 37 (IL-37) is a cytokine belonging to the IL-1 family that shows anti-inflammatory and protective effects in various mouse models of psoriasis. Even though various animal models are used to investigate the pathogenic mechanisms of psoriasis, human clinical studies are still needed to make up for the deficiencies, as animal models generally do not exhibit the complex phenotypic features of human psoriasis. Our study aims to demonstrate the relationship between IL-37-producing tissue-resident immune cells with the pathogenesis of psoriasis. The present study was performed on 28 psoriasis patients and 17 healthy volunteers. The ability of anti-inflammatory cytokine IL-37 to impede inflammation and regulate metabolic pathways was assessed by real-time quantitative polymerase chain reaction. Finally, immunofluorescence double staining for CD4+ IL-37b+ , CD68+ IL-37b+ , and (forkhead box protein P3) Foxp3+ IL-37b+ was performed. The proportion of CD4+ IL-37b+ T cells, CD68+ IL-37b+ macrophages, and Foxp3+ IL-37b+ T regulatory (Treg) cells was significantly increased in the psoriasis group compared to the control group. IL-37 gene expression was downregulated in psoriasis when contrasted to the control group. Our findings disclosed that IL-37-producing tissue-resident immune cells might be involved in the pathogenesis of psoriasis, and thus may be a therapeutic target for individuals with psoriasis.

Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Comparison of the tissue expressions of glutathione S transferase isoenzymes among patients with morphea and healthy controls: A preliminary study.

Morphea is an inflammatory connective tissue disorder, which is characterized by sclerosis in skin and subcutaneous tissues with a chronic progress. The oxidative stress in pathogenesis of sclerosing diseases was proposed in several studies with conflicting results. To explore the tissue expressions of Glutathione S transferase (GST) isoenzymes in patients with morphea and compare these expressions with healthy controls. Twenty-two morphea patients and 20 sex and age matched healthy controls were enrolled in this study. Four millimeter punch biopsies were performed from the active sclerotic plaques of morphea patients. Tissue samples of control group were obtained from nonlesional normal skin biopsy specimens. The protein expressions of GST isoenzymes were analyzed immunohistochemically. Tissue expressions of GSTP1, GSTT1, and GSTA1 isoenzymes in morphea patients were found to be significantly higher than in control tissues. There was no significant difference in GSTM1 isoenzyme expression between the two groups. The increased tissue expressions of GSTA1, GSTP1, and GSTT1 isoenzymes in morphea may represent the activated GST enzymes in response to excessive free radical formation and may also support the hypothesis of increased oxidative stress in morphea etiopathogenesis.

Caspase-3, p53 and Bcl-2 expression in basal cell carcinoma of the eyelid.

INTRODUCTION: Eyelid tumours mostly originated from skin and its appendeges. External carcinogens like UV radiation causes cell damages in the eyelid skin and contributes to carcinogenesis. Apoptosis is a very important mechanism to prevent these damage and probable neoplatic change. AIM: To compare caspase-3, p53 and Bcl-2 levels between patients with basal cell carcinoma (BCC) of the eyelid and healthy individuals. MATERIAL AND METHODS: Pathology archives from October 2012 to April 2015 were scanned for BCC biopsies of the eyelid and tissue removed during blepharoplasty and entropion procedures. A total of 36 specimens were found. The specimens were divided into two groups: BCC group and controls (consisting of eyelid tissue removed during routine blepharoplasty). The pathology specimens were then stained using p53, Bcl-2 and caspase-3 stains and the intensity of staining was graded on a 0-3 scale. RESULTS: Samples from a total of 36 patients were included in the study. Eighteen (50.0%) patients were female. There were 13 patients in the BCC group and 23 patients in the control group. The mean age was 66.0 ±10.8 years in the BCC group, and 65.61 ±11.22 years in the control group. The caspase-3 staining was lower in the BCC group than in the control group. No significant differences were found between the BCC group and the control group in terms of p53 levels or Bcl-2 levels (both of them, p = 1.000). CONCLUSIONS: The caspase-3 level was lower in the BCC group. This result suggests that these enzymes can play a significant role in carcinogenesis of eyelid BCC.

Morphea secondary to interferon beta1b injection: a case and review of the literature.

Interferon beta (IFNß) is a drug used successfully in the treatment of multiple sclerosis (MS). Although IFNß is a safe and well-tolerated drug, dermatological side effects are common. The most common dermatological adverse effect is a local reaction at the injection site. It may also cause inflammatory and immune-mediated dermatological side effects. However, morphea induced by IFNß1b injection is very rare.

Comparative differences between T1a/b and T1e/m as substages in T1 urothelial carcinoma of the bladder.

OBJECTIVE: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer and to display comparative differences between the T1a/b and T1e/m substaging systems. PATIENTS AND METHODS: This study included 106 patients with primary stage T1 urothelial bladder tumours who underwent surgery between January 2009 and December 2014. Pathologic specimens were re-evaluated to confirm the diagnosis of T1 and substaging by the same pathologist using two systems: T1a and T1b, and T1m and T1e. Age, tumour size, multiplicity, associated carcinoma in situ, tumour grade, and T1 substaging system were investigated to detect the relation between disease progression and recurrence. RESULTS: The recurrence rate was 52% for T1a (n=42) vs. 76% for T1b (n=20) (p=0.028) and 55% for T1m (n=32) vs. 62% for T1e (n=30), respectively (p=0.446). There was no significant difference between the substaging groups for disease progression: T1a (n=12, 15%) vs. T1b (n=7, 27%), and T1m (n=8, 13.8%) vs. T1e (n=11, 23%) (p>0.05). In the multivariate analysis, tumour size >3 cm (p=0.008), multiplicity (p=0.049), and substaging T1b (p=0.043) were independent predictive factors for tumour recurrence. According to the Kaplan-Meier actuarial method, recurrence-free survival was significantly different in patients with pT1a tumours compared with those with pT1b tumours (p=0.033). CONCLUSIONS: Substaging T1 provides a prediction of disease recurrence. Regarding recurrence, T1a/b substaging can provide better knowledge of disease behaviour because it is predicted as more superior than T1 m/e, and it can help in determining the requirement for early cystectomy.

Evaluation of oxidative stress via protein expression of glutathione S-transferase and cytochrome p450 (CYP450) isoenzymes in psoriasis vulgaris patients treated with methotrexate.

INTRODUCTION: Oxidative stress is the imbalance between oxidant-antioxidant systems and may play a major role in the psoriasis pathogenesis. Cytochrome (CYP) is a family of enzymes that are responsible for the metabolism of various endogenous and exogenous substances such as drug metabolism. Most importantly, the antioxidant system is the glutathione S-transferases (GST), which decrease oxidative stress by reducing oxidative products. AIM: We aimed to evaluate the expressions of isoenzymes of GST and CYP families and the beneficial role of metotrexate (MTX) in this process. MATERIAL AND METHODS: This study included 21 patients with psoriasis and 22 healthy subjects. We treated all the patients with 10-15 mg/week of MTX for minimum 12 weeks. Expressions of GST and CYP enzymes were assessed by immunohistochemical staining. RESULTS: GSTK1, GSTM1 and GSTT1 expressions were significantly higher in the psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05, respectively). In the psoriasis patients, GSTO1 expression was similar the control group. CYP1B1 and CYP2E1 expressions were significantly higher in the pre-treatment and post-treatment psoriasis tissues than in the control tissues (p < 0.05; p < 0.05; p < 0.05; p < 0.05, respectively). CONCLUSION: We found a significant increase in the tissue levels of, either expression of GST, or CYP, which has important role in drug metabolism and oxidative stress. MTX treatment resulted in marked clinical improvement, yet we found that MTX did not have any significant effect on these parameters. CYP2E1 is especially the most important enzyme for MTX metabolism since it is the primarily responsible of the toxic metabolism of various drugs. The other experimental studies involving greater number of patients and other different drug are needed to enlighten the role of oxidant and antioxidant systems and the other possible mechanisms for the pathogenesis of psoriasis.

The investigation of antimicrobial peptides expression and its related interaction with methotrexate treatment in patients with psoriasis vulgaris.

BACKGROUND: Psoriasis is a chronic, inflammatory and immune-mediated disease. Recently, the role of antimicrobial peptides (AMPs) such as human beta defensins (hBDs) in the pathogenesis of psoriasis has been investigated. We aimed to evaluate the expression profiles of hBD-1 and hBD-2 in psoriatic skin before and after methotrexate (MTX) therapy and to compare healthy controls. METHODS: Immunohistochemical expressions of hBD-1 and hBD-2 were assessed in 16 patients with psoriasis vulgaris and 20 normal skin biopsies from healthy controls. The patients were administered a 12 week of MTX and skin biopsy samples were obtained from the lesional skin of the patients pre-/posttreatment and normal body of the healthy controls. RESULTS: The median (range) Psoriasis Area and Severity Index (PASI) value was 21.6 (8.2-27.7) before the treatment whereas; 3.05 (1-23.4) after the treatment. hBD-1 expression in psoriasis patients was significantly higher as compared to the healthy controls before treatment (p < 0.01). No significant difference was observed between psoriasis patients and healthy controls in terms of hBD-2 expression before treatment (p > 0.05). No significant difference was observed between before-after MTX treatment in terms of hBD-1 and hBD-2 expression levels in psoriasis patients (p > 0.05). CONCLUSIONS: These findings suggest a role for hBD-1 in psoriasis pathogenesis. But MTX treatment does not affect on hBD-1 and hBD-2 expressions. Further studies are needed to assess the roles of these AMPs in psoriasis etiopathogenesis.

Oral mucosal involvement and petechial lesions: a SDRIFE case with unusual findings.

Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) is a type IV hypersensitivity reaction characterized by a symmetrical erythematous rash in the gluteal and intertriginous areas. SDRIFE was previously considered to be the same presentation as Baboon Syndrome, however, has been suggested to be a different entity in the recent publications. The lesions are generally maculopapular and there is no mucosal involvement. To date, no case with petechial findings and mucosal involvement has been reported in the literature. The present study reports a SDRIFE case with a symmetrical erythematous petechial rash and oral mucosal involvement after taking oral amoxicillin.

Comparison of TLR-2, TLR-4, and antimicrobial peptide levels in different lesions of acne vulgaris.

CONTEXT: Recent studies have shown that tolls like receptors (TLRs) and antimicrobial peptides (hBD-1, cathelicidin) play an important role in the pathogenesis of acne vulgaris (AV). OBJECTIVE: To evaluate and report the expression of TLR-2, TLR-4, hBD-1 and cathelicidin in different regions of skin in AV. PARTICIPANTS: This study was performed in 80 patients with AV and a control group of 20 healthy individuals. MATERIAL AND METHODS: Skin biopsies were performed from 20 papular, 20 pustular, 20 comedonal and 20 nodular lesions of patients and 20 healthy volunteers. Expression levels of TLR-2, TLR-4, hBD-1 and cathelicidin in four separate areas (epidermis, dermis, inflammation region and skin appendages) were evaluated by immunohistochemical method. Further, these parameters were compared between different skin lesions. RESULTS: A significant difference was found between the levels of staining of TLR-2, TLR-4 and hBD-1 from the epidermis, inflammation region, dermis and skin appendages (p < 0.05). Levels of cathelicidin were different in only the inflammation region (p < 0.05). The level of TLR-2 in the epidermis with nodules was lower than the papules and comedones (p < 0.05). Levels of TLR-2 in the inflammation and dermis of the cases with papules were significantly higher when compared to pustules (p < 0.05). The levels of staining of TLR-4 in the dermis with comedones were significantly lower compared to the cases with papules (p < 005). The level of hBD-1 in the epidermis region of comedones was significantly higher compared to nodules (p < 0.05). The expression of cathelicidin in the inflammation region of comedones was significantly low (p < 0.05). CONCLUSION: It is thought that TLR-2, TLR-4, hBD-1 and cathelicidin play an important role in the pathogenesis of AV and in the development of different acne types. We think that, better results could be obtained in treatment of AV with different treatment options targeted in regulation of TLR-2, TLR-4, hBD-1 and cathelicidin release.

Clinical significance of serum and urinary HER2/neu protein levels in primary non-muscle invasive bladder cancer.

OBJECTIVE: We aimed to compare serum and urinary HER2/neu levels between healthy control group and patients with non-muscle invasive bladder cancer. Additionally, we evaluated relationship of HER2/neu levels with tumor stage, grade, recurrence and progression. MATERIALS AND METHODS: Fourty-four patients with primary non-muscle invasive bladder tumors (Group 2) and 40 healthy control group (Group 1) were included the study. Blood and urinary samples were collected from all patients and HER2/neu levels were measured by ELISA method. Blood and urinary HER2/neu levels and additionally, ratio of urinary HER2/neu levels to urinary creatinine levels were recorded. Demographic data and tumor characteristics were recorded. RESULTS: Mean serum HER2/neu levels were similar between two groups and statistically significant difference wasn't observed. Urinary HER2/neu levels were significantly higher in group 2 than group 1. Ratio of urinary HER2/neu to urinary creatinine was significantly higher in group 2 than group 1, (p=0,021). Serum and urinary HER2/ neu levels were not associated with tumor stage, grade, recurrence and progression while ratio of urinary HER2/neu to urinary creatinin levels were significantly higher in high-grade tumors. HER2/neu, the sensitivity of the test was found to be 20.5%, and the specificity was 97.5%, also for the urinary HER2/neu/urinary creatinine ratio, the sensitivity and specificity of the test were found to be 31.8% and 87.5%, respectively. CONCLUSIONS: Urinary HER2/neu and ratio of urinary creatinine urine were significantly higher in patients with bladder cancer compared to healthy subjects. Large series and controlled studies are needed for use as a tumor marker.

A comparative study of histopathological findings in skin biopsies from patients with psoriasis before and after treatment with acitretin, methotrexate and phototherapy.

INTRODUCTION: Psoriasis is a chronic and inflammatory skin disease. Few studies in the literature evaluate the responses to the treatment histopathologically. OBJECTIVES: In this study, we evaluated and compared skin biopsies taken from patients with psoriasis before and after phototherapy and therapy with acitretin and methotrexate. MATERIAL AND METHODS: We included 64 patients with a diagnosis of psoriasis vulgaris in our study. We performed phototherapy on 33 patients (51.6%), while 19 patients (29.7%) were treated with methotrexate and 12 patients (18.8%) were treated with acitretin. RESULTS: All of the patients had chronic plaque psoriasis, and they had skin lesions on more than 10% of their total body surface area and a score of PASI of 7.2-21.8 (average: 12.2). The histopathological parameter scores were similar in the initial evaluations of the pre-treatment treatment groups. When the biopsy specimens of all cases were evaluated together, a significant decrease was observed in terms of parakeratosis, Munro's microabscesses, regular acanthosis, pustules of Kogoj, lymphocyte infiltration in the papillary dermis, loss of the granular layer, spongiosis, suprapapillary thinning, vascularity in the papillary dermis and neutrophile infiltration in the papillary dermis. CONCLUSION: We found in our study that conventional treatment modalities provided histopathologically significant recovery in psoriasis, but they did not have an effect on some histopathological findings. To our knowledge, it is one of the few studies to assess these parameters in psoriasis under the continuous effect of acitretin, methotrexate and phototherapy for three months. There is a need for studies with larger series to examine the histopathological effects of these treatment modalities in terms of immunopathology.

Ber-EP4 staining patterns on basal cell carcinomas.

OBJECTIVE: This article aimed to study two different parameters of basal cell carcinoma (BCC): First, to analyze the expression of antihuman epithelial antigen (Ber-EP4) on the primary and recurrent BCCs on the head, neck, and other body parts and second, to find Ber-EP4's staining pattern and staining intensities correlation between histological type, demographic data, tumor, and its prognostic parameters. METHODS: We evaluated the Ber-EP4 staining patterns of 201 patients diagnosed with BCC. We analyzed the possible correlation between the tumor's prognostic parameters and the Ber-EP4 staining intensity and its pattern (peripheral, superficial, or diffused). RESULTS: In 199 out of the 201 cases, staining was observed. Two cases were unstained. In 25.6% (n=51) of the cases with staining, the staining was weak, on the 25.6% (n=51), it was moderate, and on the 48.8% (n=97), it was severe. The staining pattern was 31.2% (n=62) peripheral, 4.0% (n=8) superficial, 54.7% (n=109) diffuse, and 10.1% (n=20) peripheral and superficial. CONCLUSION: Ber-EP4 is the only antibody commonly used for BCC diagnosis; the existence of different staining intensities and patterns in BCC tumor cells in routine dermatopathology practice limit the pathologists. The studies investigating Ber-EP4 staining in BCCs were conducted with very small numbers of cases. In these studies, even the presence of staining in the focal area was considered to be a positive acceptance criterion; the staining intensity and pattern were not evaluated. Therefore, our study is the first study with a high number of cases and the first to include an evaluation of Ber-EP4 staining's intensity and localization.

Investigation of low and high dose rate X-ray effects on histopathological changes and prognostic importance of Ki-67 in laryngeal cancer radiotherapy.

The aim of this study is to analyze the effect on histopathological changes and Ki-67 expression levels of Flattening Filter (FF) and Flattening Filter Free (FFF) beams to investigate the radiobiological mechanisms underlying laryngeal cancer (LCa) post-radiotherapy (RT) on mice models. Forty adult NOD SCID gamma (NSG) mice models were randomly divided into four groups; the sham, LCa, FF-RT and FFF-RT groups. The head and neck region of mice in FF-RT and FFF-RT groups (LCa plus RT groups) were irradiated with a single dose of 18 Gy at 400 MU/min and 1400 MU/min. The NSG mice received radiotherapy 30 days after tumor transplantation and sacrificed 2 days after radiotherapy for analysis of histopathology parameters and K-67 expression levels. Comparing the LCa, FF-RT and FFF-RT groups with the sham group, statistically significant differences were observed in histopathological parameters depending on tumor tissue and dose rate (p < 0.05). When the histopathological effects of FF-RT beam on LCa tissue were compared with FFF-RT beam, it was observed that statistically significant differences occurred (p < 0.05). Comparing the LCa group with the sham group, it was observed that the Ki-67 level affected significantly depending on the development of cancer (p < 0.01). It was concluded that FF and FFF beams caused significant changes in the histopathological parameters and Ki-67 expression levels. When the effects of FFF beam on Ki-67 levels, cell nucleus and cytoplasmic findings were compared with FF beam, significant radiobiological differences were observed.

Evaluation of histopathological changes in control biopsies which taken 48 sessions after NBUVB phototherapy for early-stage mycosis fungoides.

BACKGROUND: There are not many studies investigating histomorphological changes in 48 sessions in patients with early-stage MF after narrowband UVB (NBUVB) treatment. Our purpose is to evaluate histological features of phototherapy after 48 sessions and determine which parameters are more reliable for controlling skin biopsies. METHODS: Biopsies of 32 patients with early stage of MF, who were treated with NBUVB phototherapy, were histologically evaluated before and after the treatments, including epidermotropism, stratum corneum, epidermal thickness, dermal infiltration, papillary dermal fibrosis, vascular alterations, and other dermal changes. We discuss the histomorphological effects of NBUVB phototherapy on skin biopsies by comparing the responders with nonresponders, with before and after the treatment. RESULTS: 9 patients (28%) did not give any response to treatment. Alleviation in epidermotropism, increases in parakeratosis and normal keratosis, perivascular infiltration, and melanophages, decrease in the lichenoid/patchy lichenoid infiltration pattern after the treatment was statistically significant. Comparing by response, normalization of stratum corneum and epidermis, orthohyperkeratosis, decrease in linearly arranged cells, the lichenoid/patchy lichenoid infiltration, the loss of inflammation were statistically significant in responders group. CONCLUSION: We detected a significant decrease in linearly arranged cells after phototherapy, indicating that it is an "important diagnostic parameter" in evaluation of therapeutic response.

Clinicopathological Features of Cutaneous Findings of SARS-CoV-2 Infection.

Objective: In December 2019, severe acute respiratory syndrome coronavirus-2, which emerged in Wuhan, China, spread rapidly and created a pandemic. Coronavirus disease-2019 (COVID-19) can affect different organ systems, including the skin. Recently, COVID-19 cases with skin lesions of different clinicopathological features have been published. This study aimed to present the histopathological features of 19 COVID-19 cases with cutaneous findings and discuss them in light of the literature. Methods: Skin biopsy specimens of 19 patients with skin rashes associated with COVID-19 were evaluated histopathologically and clinically. Results: Clinical manifestations of rashes developed in eight female, seven male, and four pediatric patients with COVID-19. Urticaria/urticarial vasculitis (n=7), maculopapular eruption (n=7), panniculitis (n=2), purpuric eruptions (n=2), and livedoid-like lesions were noted. Histopathologically, besides the inflammatory findings, the most striking feature was that the vessels were more or less affected in almost all cases. Conclusions: Cutaneous lesions associated with COVID-19 are increasingly being reported. We believe that every data presented about this disease, which has many unknowns, will shed light on future research. Every case can lead us a new way.

Tissue expression of glutathione S transferase isoenzymes in vitiligo.

The association of glutathione S-transferase (GST) enzymes with vitiligo is inconclusive. To evaluate tissue expressions of GST isoenzymes in vitiligo patients and to compare these expressions with healthy controls, we used 26 active depigmented patches on the trunk of vitiligo patients and 20 healthy sex and age matched controls. Punch biopsies were taken from the lesioned or normal skin. Tissue expression of GST isoenzymes were analyzed immunohistochemically. Tissue expression of GSTT1, GSTA1 and GSTP1 was significantly higher in the patient group than controls. Tissue expression of GSTM1 was not significantly different between the two groups. The increased tissue expression of GSTT1, GSTA1 and GSTP1 may represent a response to excess free radical formation in vitiligo and may support the role of oxidative stress in the pathogenesis of vitiligo.

Relation of beclin-1 and bcl-2 expressions with pathological parameters and prognosis in clear cell renal cell carcinomas.

INTRODUCTION: The most common type of renal cancers is the clear cell renal cell carcinoma (CCRCC) and 98% of CCRCCs have a loss of sequence in the short arm of chromosome 3 by deletion or translocation. Programmed cell death; another possible mechanism of tumorigenesis, comprises two separate components: apoptosis and autophagy. This study aims to show the rela-tion between the prognostic parameters and survival, and Beclin-1, as the representative marker of autophagy, and Bcl-2 as the representative marker of apoptosis in CCRCC patients. In this study, we aimed to determine if Beclin-1 and Bcl-2 expression levels can provide any prognostic information about CCRCC patients. METHODS: We examined a total of 84 patients who underwent partial or radical nephrectomy and were diagnosed as having CCRCC between January 2008 and December 2015. Immunohistochemical staining was performed, the evaluation was for Beclin-1 and Bcl-2 semi-quantitative, and based on the percentage of positively stained cells (proportion) and staining intensity. RESULTS: There was only a statistical significance between Beclin-1 expression and age (r:-0.274; p=0.012; p <0.05). There was a marginal significance between ISUP grade and Beclin-1 (p=0.051). The relation of Bcl-2 expression with the ISUP grade, recurrence, metastasis, and mortality revealed statistical significance (p=0.001, p=0.019, p=0.009, p=0.013, respectively). The ISUP grade and the Bcl-2 expression revealed statistical significance on multivariate analysis ( HR 7.453, 95% CI: 1.935-28.713, p=0.004). The 5-year and 10-year tumor recurrences rates were lower in Bcl-2 positive group, and Bcl-2 positive group experi-enced longer disease free and overall survival. CONCLUSION: There was only marginal correlation between Beclin-1 expression and ISUP grade. No other histopathologic prog-nostic parameters histologic parameters revealed any signigificance. The higher expression of Bcl-2 is correlated with nuclear lower ISUP grade, lower pT stage, and longer disease free and overall survival.