Expression of Autophagy Markers Beclin1 and LC3B in Prostatic Carcinoma: An Immunohistochemical Case-Control Study.

BACKGROUND & OBJECTIVE: Prostatic carcinoma represents the second most common cancer diagnosed in men worldwide after lung cancer and the fourth common male malignancy in Egypt. Autophagy is a natural process that has both oncogenic and tumor-suppressive activities. This study aimed to evaluate the role of Beclin1 and LC3B in prostatic carcinoma. METHODS: This retrospective case-control study was conducted on 110 prostate biopsies divided into three groups (55 prostatic carcinomas, 45 pure benign prostatic hyperplasias (BPH), and 10 BPH with adjacent prostatic carcinoma) retrieved from the archive of the Pathology Department, Faculty of Medicine, Menoufia University, in the period between 2017 and 2020. All biopsies were stained for Beclin1 and LC3B antibodies. RESULTS: There was a highly significant association between higher Beclin1 and LC3B immunoreactivity score and Gleason score (score 8 and 9) (P=0.002 and 0.000, respectively). Moreover, there was a highly significant direct association between Beclin1 and LC3B expression (r=0.52, P=0.000). Also, there was a significant stepwise increase in Beclin1 positivity among the three studied groups starting from BPH to prostatic carcinoma passing through cases of BPH with neighboring tumor (P=0.000). CONCLUSION: From the results obtained in the present study, autophagy markers Beclin1 and LC3B showed upregulation in prostatic carcinoma. Moreover, both were associated with poor prognostic factors. So, it might be necessary to control autophagy flux in prostatic carcinoma. This might be one of the future therapeutic targets for the management of prostatic carcinoma.

Immunohistochemical expression of cornulin in lesional and perilesional skin of plaque psoriasis.

BACKGROUND: Psoriasis is an immune-related disease with dermal inflammation and epidermal hyperplasia. Cornulin has a significant role in keratinocyte proliferation and stimulates inflammation in psoriasis. AIM OF THE WORK: This work aims to evaluate Cornulin expression values in lesional and perilesional psoriatic skin compared with the control group's skin through immunohistochemistry. METHODS: This case-control study included 30 cases with plaque psoriasis and another 30 as controls. Patient samples were collected, and immunohistochemical staining of Cornulin was conducted. RESULTS: In the epidermis, there was a stepwise pattern of significant Cornulin overexpression in keratinocytes starting from controls (34.00 ± 23.65) to lesional (62.59 ± 23.93) passing through perilesional skin (36.52 ± 18.49) (p < 0.001). Moreover, there was also a stepwise pattern of the significance of Cornulin starting from 4 in controls (13.3% for both) to 28 lesional cases (93.3%) and 18 (60.0%) passing through 17 perilesional skin cases (56.7%) and 5 (16.7%) (p < 0.001 for both) for inflammatory cells and adnexa, respectively. A significant relationship between lesional epidermal Cornulin's strong intensity and a higher H-score and both hyperkeratosis and parakeratosis was found (p = 0.008 for both intensity and 0.028 for both H-scores). CONCLUSION: Cornulin might be implicated in keratinocyte hyperproliferation and inflammation in plaque psoriasis and may be valuable as therapeutic target.

Hepatocellular Carcinoma Score and Subclassification Into Aggressive Subtypes Using Immunohistochemical Expression of p53, ß-Catenin, CD133, and Ki-67.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy in adults. Several studies have classified HCC into molecular subtypes aiming at detecting aggressive subtypes. The aim of the present study was to investigate the role of p53, ß-catenin, CD133, and Ki-67 in subclassification of HCC into different aggressive subtypes and the correlation between those markers and the clinicopathologic characteristics of HCC patients. This retrospective study was conducted on paraffin-embedded blocks of 114 HCC specimens. Tissue microarray was constructed and immunostaining for p53, ß-catenin, CD133, and Ki-67 was performed and HCC score was formulated. P53 expression was associated with old age (P=0.028), large tumor size (P=0.019), poorly differentiated HCC (P=0.012), hepatitis B virus (HBV) positivity (P=0.032), and hepatitis C virus (HCV) negativity (P =0.046). ß-catenin expression was associated with small sized tumors (P=0.005), HBV negativity (P=0.027), early-staged tumors (P=0.029), and prolonged recurrence-free survival (P=0.045). High percentage of CD133 expression was associated with old patients (P=0.035) and HBV positivity (P= 0.045). Ki-67 expression was associated with large tumor size (P= 0.049), vascular invasion (P= 0.05), old age (P=0.035), and previous treatment of HCV by direct acting antiviral agents (P=0.005). Cases with high HCC score showed significant association with old patients (P=0.002), previous treatment of HCV by direct acting antiviral agents (P<0.001), large tumor size (P<0.001), and poorly differentiated tumors (P= 0.009). The proposed HCC score can divide HCC patients into subtypes necessitating tailoring of treatment strategy according to this proposed score to target and optimally treat the aggressive subtypes. This score needs to be further validated on large number of patients with longer follow-up period.

The Profile and Role of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: An Immunohistochemical Study.

Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. Tumor-infiltrating lymphocytes (TILs) are a class of cells that form the tumor microenvironment and thus have an effect on carcinogenesis. The aim of this study was to investigate the immunohistochemical expression of CD8, CD4, cytotoxic T lymphocyte-associated protein-4 (CTLA-4), and granzyme B in HCC and their correlation with clinicopathologic parameters and prognosis. This study was carried out on 112 cases of HCC. High percentage of CD8+ TILs was associated with large tumors and adjacent noncirrhotic liver. High percentage of CD4+ TILs and high CD4 to CD8 ratio were associated with nonviral etiology, low alpha fetoprotein, and direct acting antiviral treatment. High percentage of CTLA-4-positive TILs tended to be associated with high-grade HCC, while a high percentage of CTLA-4 in tumor cells was associated with multiple lesions and low tumor grade. High percentage of granzyme B+ TILs was associated with low grade, early stage, and absence of tumor recurrence. High CD4 percentage and high CD4/CD8 ratio affected patients' overall survival. There is a dynamic interaction between the different subsets of lymphocytes in the environment of HCC manifested by coparallel expression of CD4 and CD8 augmenting the expression of CTLA-4, and only CD8 augments the expression of granzyme B. This opens the gate for the beneficial role of immunotherapy in the management of HCC, reducing recurrence and improving survival.

The Diagnostic Role of SPINK1 in Differentiating Hepatocellular Carcinoma From Nonmalignant Lesions.

BACKGROUND AND AIM: Distinction of small-sized hepatocellular carcinoma (HCC) from dysplastic nodules may be difficult. In addition, distinction of well-differentiated HCC (WD-HCC) from high-grade dysplastic nodule (HGDN) is also difficult in small needle biopsy. We aimed to study serine peptidase inhibitor, Kazal type 1 (SPINK1) immunohistochemical expression in HCC to differentiate it from nonmalignant lesions. METHODS: This study included 179 specimens from the archival material of Pathology Department, National Liver Institute, Menoufia University, between 2007 and 2014, divided as 93 HCC and 86 nonmalignant lesions. All cases were stained for SPINK1 antibody. RESULTS: SPINK1 was expressed in 76.3% of HCC cases with a diagnostic accuracy of 79.3%.There was a significant difference between focal nodular hyperplasia and WD-HCC cases regarding mean value of SPINK1 expression (P=0.015). In addition, there was low SPINK1 score in cirrhosis cases compared with WD-HCC. Moreover, there was a high significant difference between WD-HCC and HGDN regarding SPINK1 expression (P=0.001), with 83.3% sensitivity and 84.6% specificity. CONCLUSIONS: SPINK1 can be used to differentiate between a WD-HCC and a HGDN with high diagnostic validity.