الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Renal cell carcinoma is a heterogeneous group of cancers originating from the renal tubular epithelial cells. The most common is the clear cell type, followed by papillary and chromophobe RCCs.
The global burden of RCC is projected to continue to rapidly increase. RCCs represent the most common renal tumor in adults and are divided into a number of different histological types Tumor type also has utility in selection of patients for adjuvant therapy, further underlining the importance of assigning tumors to the correct category on pathological assessment.
The prognosis of RCC depends on many factors such as anatomical prognostic factor is the tumour size, lymph node status and metastasis.
Other prognostic factors comprises tumour grade, subtype, presence of sarcomatoid or rhabdoid features, microvascular invasion, and tumour necrosis. Recently the identification of molecular markers has led to new insights into RCC biology and the development of novel targeted therapies.
Galectins are soluble proteins that are widely expressed in various cell types and mediate their functions both intracellularly and extracellularly. Due to the diverse functions of galectins, such as in apoptosis, angiogenesis, cell migration and tumor-immune escape, altered levels have been implicated in cancer biology. Galectin-1 is a prototype galectin with one carbohydrate recognition domain. Galectin-1 is expressed in some malignant tumours and is involved several biological activities, including cell adhesion, cell migration, cell apoptosis, cell proliferation, regulation of immunity, and tumour angiogenensis.
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Decreased expression of Galectin-1 has been associated with tumor invasiveness & lymph node metastasis in some tumors as bladder carcinoma & lung adenocarcinoma. However, increased expression was proved to be associated with poor prognosis in other tumors such as osteosarcoma & breast carcinomas. Galectin-3 is the only chimera galectin; it has a C-terminal carbohydrate recognition domain as well as an N-terminal tail. Galectin-3 was found in a relatively large spectrum of human tumors, but with a heterogenous expression that varied between different organ tissues. For instance, Galectin-3 expression was reported to be increased in stomach, head and neck, pancreas, thyroid gland, colon and small-cell lung cancer, while a low expression of this protein was found in uterus, prostate and breast cancer.
The present work aimed at studying the expression of Galectin-1 and Galectin-3 in three major histologic RCC subtypes as well as their correlation with the clinicopathological parameters. In addition to that, comparing the expression of Galectin-1 and Galectin-3 between the tumor tissue and adjacent free renal tissue.
The present work has been carried on sixty cases of the three main histologic subtypes of RCC. All cases were collected retrospectively from the archive of the pathology department at Medical Research Institute (MRI), Alexandria University, in the period between 2018-2020.
Serial of 5-um thick paraffin sections were cut from each block and have been subjected to:
1. Routine H&E stain: to review the pathology and the different histologic parameters.
2. IHC staining for Galectin-1 and Galectin-3.
The expression of both Galectin-1 & Galectin-3 was detected as homogenously brown cytoplasmic staining. The cases were classified into two groups; negative Galectins expression (<50% of tumor cells shows galectins positivity) & positive Galectins expression (50% and more of tumor cells are positive for galectins).
Results showed that Galectin-1 is highly expressed in the renal tumor tissue in comparison to the adjacent free renal tissue with a statistically significant result ( p value<0.001 ); while the case was opposite regarding Galectin-3 being expressed more in
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the adjacent free renal tissue with a statistically significant result ( P value <0.002). This finding suggests a tumor promoter role for Galectin-1 and a tumor suppressor role for Galectin-3.
Also there was a statistically significant association between Galectin -1 & 3 expression and the tumor histological subtypes with p values (0.03) and (0.011) respectively. The expression of both Galectins was different among the different histological subtypes of RCC being highly expressed in chromophobe subtype more than the clear & papillary subtypes. This finding suggests that these markers could be used as potential diagnostic markers for this subtype.
There was an inverse statistically significant association between Galectin-1 expression in the tumor tissue and microvascular LVI (p value 0.003).
There was no statistically significant association found between Galectin-1 expression and clinicopathological parameters like age, sex, side, site, size, stage, nuclear grade, hemorrhage, necrosis, capsular, perinephric & sinus fat infiltration as well as the immune response
There was a statistically inverse significant association between Galectin-3 expression in the tumor tissue and presence of hemorrhage and necrosis (p value 0.021 & 0.040) respectively predicting an anti-necrotic role for Galectin-3. There was a statisitcially significant association between Galectin- 3 expression and tumor size as well (p value 0.203).
There was no any statistically significant association between Galectin-3 on one hand and the remaining clinicopathological parameters on the other hand as age, sex, side, site, size, stage, nuclear grade, capsular, perinephric & sinus fat infiltration as well as the immune response & LVI.
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6.2. Conclusions:
Galectin-1 could be considered as a tumor promoter in RCC being expressed in the tumor tissue more than the adjacent normal tissue.
Galectin-3 could be considered as a tumor suppressor protein in RCC being expressed in the adjacent normal tissue more than the tumor tissue.
Galectin-1 & Galectin-3 could be used as a potential diagnostic markers for chromophobe renal cell carcinoma being highly expressed in this subtype in comparison to others, however further studies are needed to prove this.
Galectin-3 has an anti-necrotic role and this explains why tumors with high Galectin-3 expression show resistance to chemotherapeutic agents.
Galectin-1 & Galectin-3 could be used as potential molecular targets for RCC therapy.
6.3. Recommendations:
Studying the expression of both Galectin-1 & Galectin-3 on a larger scale incorporating cases with different histological & molecular subtypes as well as the new emerging entities of RCC.
Studying the expression of both Galectin-1 & Galectin-3 using different molecular techniques such as PCR & gene sequencing to elaborate their roles and strengthens the achieved results.
Further study of the expression of Galectin-1 & Galectin-3 in a larger sample size including both types of papillary renal cell carcinoma and comparing their expression between these two heterogeneously different types.
Incorporating cases showing distant metastasis and comparing the expression of both Galectins in the primary & metastatic tissue to study the proposed roles of both Galectins throughout the carcinogenic pathway of RCC.