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.

Genetic Polymorphism of Epidermal Growth Factor Gene as a Predictor of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients.

BACKGROUND: In Egypt, the incidence of hepatocellular carcinoma (HCC) is approximately 4.7% of chronic liver disease patients due to (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration. A functional polymorphism in EGF 61A>G was identified; itwas associated with higher risk of HCC. OBJECTIVES: to investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV) cirrhotic patients as well as its relation to EGF protein expression in HCC tissue. PATIENTS AND METHODS: this casecontrol study was conducted on 75 HCV cirrhotic patients including 50 HCC patients (25 withresectable HCC and 25 with advanced unresectable HCC) and 25 healthy persons were included. EGF genotype was detected by restriction fragment length polymorphism. EGF expression in HCC tissue biopsiesfrom patientswhounderwent surgical resection was done by immunohistochemical examination. RESULTS: The GG genotype was associated with significant increased risk of HCC compared to AA genotypes (P=0.031) in cirrhotic group. The G allele had a highly significant risk of HCC compared to allele Ain recessive model GG vs. AG+AA (P=0.036) rather than in the dominant model GG +AG vs. AA (P=0.66). There was significant increased expression of EGF in tumour tissues in patients with GG genotype compared to AG genotype and AA genotype p= 0.019. CONCLUSION: EGF gene polymorphism (GG genotype) had a significant risk of HCC development in cirrhotic patients. This is confirmed by increased EGF expression in liver tumor tissue from HCC patients.
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Is Aquaporin-3 a Determinant Factor of Intrinsic and Extrinsic Aging? An Immunohistochemical and Morphometric Study.

Aquaporin-3 (AQP3) is an aquaglyceroporin that plays a role in skin hydration, cell proliferation, and migration. The aim of this work was to investigate the expression of AQP3 in sun-exposed and sun-protected human skin from different age groups to understand the relationship between AQP3 and skin aging. Using standard immunohistochemical techniques, sun-exposed and sun-protected skin biopsies were taken from 60 normal individuals. AQP3 was expressed in the basal and the suprabasal layers, sparing the stratum corneum, in all specimens. Dermal expression was detected in fibroblasts, endothelial cells, and adnexa. Sun-protected skin showed a significantly higher epidermal H-score and percentage of expression (P=0.002 and <0.001, respectively) compared with sun-exposed skin. The AQP3 expression intensity showed a gradual decrease from the 20 to 35-year-old group to the 35 to 50-year-old group, with the least immunoreactivity in the above 50-year-old group. A significant difference was detected in the H-score in favor of the 20 to 35-year-old group in sun-exposed and sun-protected skin (P<0.001 for both). A significant negative correlation was noted between the AQP3 expression percentage and the age in sun-exposed (r=-0.64, P<0.001) and sun-protected skin (r=-0.53, P<0.001). In conclusion, the skin dryness observed in intrinsic and extrinsic aged skin may be explained, at least in part, by AQP3 downregulation. This may open new avenues sufficient to control skin texture and beauty. Its interaction in skin protein organization and gene polymorphism can also be tackled in future research. In addition, clinical trials using AQP3 topical applications should be carried out to evaluate its effectiveness in the reversal of age-related skin changes.

The Role of Hepsin in Endometrial Carcinoma.

PURPOSE: Endometrial carcinoma is the sixth most common cancer in women worldwide and the most common invasive cancer of the female genital tract in developed countries. It is hoped that through a better understanding of the alterations implicated in endometrial cancer pathogenesis and prognosis, a more complete profile of risk factors and targeted therapy can be developed. Hepsin is a member of the type II transmembrane serine protease family. The importance of hepsin in prostate cancer has been demonstrated by several studies. However, the role of hepsin in endometrial carcinoma is yet to be identified. This study aimed to evaluate the immunohistochemical expression of hepsin in endometrial carcinoma, trying to explore its diagnostic and prognostic value. MATERIALS AND METHODS: This retrospective study was conducted on 27 endometrial carcinoma and 18 endometrial hyperplasia cases. Immunohistochemical expression of hepsin was evaluated in tissue specimens and results were correlated with the available clinicopathlogic parameters. RESULTS: Positive hepsin expression was seen in all (100%) carcinoma and 17/18 (94.44%) endometrial hyperplasia cases. The H-score of hepsin expression in endometrial carcinoma was significantly higher than that of hyperplasia cases (P=0.012). A significant negative association was found between hepsin expression in endometrial carcinoma cases regarding the grade and the size of tumors (P=0.018 and 0.008, respectively) as well as myometrial invasion (P=0.027). CONCLUSIONS: Hepsin could play an important role in the pathogenesis and the early carcinogenesis of endometrial carcinoma and could serve as a prognostic biomarker in this tumor.

The Predictive and Prognostic Role of Topoisomerase IIα and Tissue Inhibitor of Metalloproteinases 1 Expression in Locally Advanced Breast Carcinoma of Egyptian Patients Treated With Anthracycline-based Neoadjuvant Chemotherapy.

PURPOSE: Locally advanced breast cancer (LABC) is a heterogeneous entity that remains a clinical challenge. Anthracycline-based neoadjuvant chemotherapy has emerged as the standard of care for those patients. However, it is associated with serious side effects including cardiotoxicity. This study aimed to evaluate the prognostic and predictive role of topoisomerase IIα (TOP2α) and tissue inhibitor of metalloproteinases 1 (TIMP-1) in Egyptian LABC patients after anthracycline-based neoadjuvant chemotherapy. MATERIALS AND METHODS: This retrospective study was conducted on 84 LABC cases. Immunohistochemical expression of TOP2α and TIMP-1 was evaluated in pretreatment needle core biopsies. Results were correlated with clinicopathlogic parameters, response to neoadjuvant chemotherapy in postoperative specimens, disease-free survival and overall survival (OS). RESULTS: Positive TOP2α expression was detected in 57/84 (67.9%) cases. It was significantly associated with good response to chemotherapy in breast (P=0.048) and lymph node (P=0.06) as well as prolonged OS (P=0.04). It tended to be the most independent prognostic factor for OS (P=0.06). Positive TIMP-1 expression was detected in 48/84 (57.1%) cases. It was significantly associated with poor response to chemotherapy in breast (P=0.02). The 2T profile (TOP2α+ and TIMP-1-) was significantly associated with good response to chemotherapy in breast (P=0.006). CONCLUSION: TOP2α and TIMP-1 are important predictive and prognostic factors in LABC patients who received anthracycline-based chemotherapy.

Immunohistochemical expression of TGF-ß1 in lichen planus.

BACKGROUND: Lichen planus (LP) is a chronic recurrent rash of unknown cause with no established cure. Clinical and immunohistochemical studies strongly support an immunologic basis for the disease. There has been growing evidence suggesting a role for transforming growth factor ß1 (TGF-ß1) in the pathogenesis of LP. OBJECTIVE: The aim of the present study was to investigate the possible role of TGF-ß1 in the pathogenesis of LP. MATERIALS AND METHODS: TGF-ß1 was analyzed on skin biopsies of 25 patients presenting with LP and 10 age-matched and sex-matched normal subjects (controls). RESULTS: TGF-ß1 was expressed in keratinocytes of 70% of the control group and 48% of LP cases with a significant difference in intensities of expression (P=0.01). In LP, moderate intensity of keratinocyte expression was significantly associated with frequent apoptosis (P=0.04). Dermal lymphocytes showed positive expression in 80% and intense expression was significantly associated with absent hyperkeratosis (P=0.03). Only 2 cases showed mild expression in epidermal lymphocytes. CONCLUSIONS: Reduced TGF-ß1 expression in LP may participate in immune dysregulation of the disease.