The Role of Maspin (Mammary Serine Protease Inhibitor) in Colorectal Carcinoma, an Immunohistochemical Study

Colorectal carcinoma (CRC) ranks as the third most common cancer worldwide, significantly contributing to cancer-related deaths and increasingly affecting younger populations .CRC develops when stem cells present at the base of the colon crypts undergo genetic and epigenetic modifications which affect oncogenes and tumour suppressor genes, leading to the transformation of normal stem cells to cancerous stem cells .Tumor suppressor genes( TSGs) : are genes involved in DNA damage repair, inhibition of cell division, induction of apoptosis, and suppression of metastasis . Maspin(mammary serine protease inhibitor) is a protease inhibitor of the serpin family, known to have tumor suppressor activity .maspin was called a multifaced protein, because it interacts with diverse groups of intercellular and extracellular proteins, and regulates cell adhesion, motility, apoptosis, and angiogenesis.Maspin expression has been demonstrated in multiple tissues including epithelium of the breast, prostate. Depending on the cell type, maspin also demonstrates a broad localization pattern. In mammary epithelial cells, maspin localizes primarily to the cytoplasm, but can also localize to the nucleus (in myoepithelial cells), secretory vesicles, and the cell surface. The localization of maspin appears important to its function(s) since in some tissues, aberrant maspin localization can be indicative of a neoplastic lesion. demonstrated that the cytoplasmic localization of maspin in ovarian carcinoma coincided with a poor prognosis, whereas nuclear maspin localization in these cancers was indicative of a more benign lesion, suggesting an important tumor-suppressive r role for nuclear maspin. Maspin has two opposing roles in cancer, it acts as a tumor suppressor that is down-regulated in gastric, breast versus an oncogenic role as it is over-expressed in gall bladder carcinoma.

Its role as tumor suppressor gene occurs through promoter hypomethylation and histone acetylation. On the contrary, maspin promoter methylation is associated with maspin tumor suppressor gene silencing and oncogenic potentiation. To our knowledge,few studies assesed the prognostic role of maspin in colorectal carinoma . Investigators reported that the prognostic role of maspin depend on it's subcellular localization as the cytoplasmic maspin positivity is considered as an indicator of low metastatic risk and late recurrence but nuclear positivity is correlated with early recurrence after surgery, especially for advanced stage carcinomas. study will include 50 formalin-fixed parrafin embedded blocks of Colorectal carcinoma cases . Colectomy specimens will be obtained from the archive of the Surgical Pathology Laboratory Assiut University Hospital, Faculty of Medicine. The cliniopathological features will be obtained from the hospital medical records, including patient age, gender, tumor site, tumor size . Representative hematoxylin and eosin-stained slides of tumor will be examined for each specimen for identification of the following features: histologic type and grade according to WHO( World Health Organization) classification of colon and rectal tumors, 5th edition, 2019) , lympho-vasular(LVI) and perineural invasion (PNI),depth of tumor invasion, lymph node metastasis, pathologic stage (according to TNM classification of the American Joint Committee on Cancer (AJCC) 8th edition. Immunohistochemical staining:Tissue sections of 4 µm thickness of formalin-fixed paraffin-embedded specimens will be taken from tissue blocks. Sections will be deparaffinized in xylene and rehydrated in a descending graded ethanol series. The endogenous peroxidase will be blocked with 6% hydrogen peroxide. For epitope retrieval, sections will be microwaved in citrate buffer, pH 6. Then sections will be incubated with the primary antibodies (Maspin) Then the Secondary staining kits were used according to the manufacturers instructions