الفهرس 
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Abstract
The present study comprised 70 formalin-fixed, paraffin-embedded tissue specimens of invasive duct breast carcinoma NOS. They were randomly selected and retrieved from the archives of histopathological laboratories of Minia Oncology Centre, in the period between 2014 and 2019. In addition, 25 metastatic malignant lymph nodes for lymph node positive cases were also included in the study. We studied the immunohistochemical expression of Snail 1 and OCT4 in these cases.
Snail 1 immunostaining was nuclear. High Snail 1 expression was detected in 52.86% of cases. High Snail 1 expression was significantly associated with larger tumor size, higher tumor grade, higher lymph node stage, higher LNR, advanced tumor stage, poor Nottingham prognostic index (NPI), high Ki-67 PIs, high HER2 neu expression, negative ER hormonal receptors, negative PR hormonal receptors and aggressive molecular subtypes being highest in triple negative and HER2 enriched types. (P= 0.028, 0.003, 0.024, 0.002, 0.001, 0.001, 0.001, 0.011, 0.002, 0.001, 0.002 respectively). No significant changes were found between Snail 1 expression in the primary tumor and their corresponding lymph node metastasis.
OCT4 immunostaining was either cytoplasmic or nuclear. Regarding cytoplasmic expression of OCT4, high cytoplasmic expression was detected in 38.57% of the cases. High cytoplasmic OCT4 expression was significantly associated with some of poor prognostic factors of IDC-NOS such as higher tumor grade, higher lymph node stage, higher LNR, advanced tumor stage, poor NPI, high Ki-67 PIs, high HER2 neu expression, and aggressive molecular subtypes being highest in HER2 enriched types (P= 0.031, 0.018, 0.003, 0.014, 0.001, <0.001, 0.001, 0.002 respectively). No significant changes were found between cytoplasmic OCT4 expression in the primary tumor and their corresponding lymph node metastasis
Summary, Conclusions and Recommendations
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Regarding nuclear OCT4 expression, high expression was detected in 21.34% of the cases. High nuclear OCT4 expression was significantly associated with poor prognostic features of the tumor such as higher tumor grade, larger tumor size, higher lymph node stage, higher LNR, advanced tumor stage, poor NPI, high Ki-67 PIs, negative ER, negative PR hormonal receptors and aggressive molecular subtypes being highest in HER2 enriched and triple negative types (p=0.044, <0.001, 0.002, 0.002, 0.002, 0.003, 0.002, 0.005, 0.009, 0.009 respectively). No significant changes were found between nuclear OCT4 expression in the primary tumor and their corresponding lymph node metastasis
A high significant positive correlation was found between Snail 1 expression and cytoplasmic OCT4 expression (r=+0.445 and p<0.001). But no significant correlation was found between Snail 1 expression and nuclear OCT4 expression. Combined Snail 1high/cytoplasmic OCT4high and Snail 1high/nuclear OCT4high immunophenotypes were significantly associated with some of the poor prognostic factors of IDC of the breast.
High Snail 1, high cytoplasmic OCT4, high nuclear OCT4 expression, combined Snail 1high / cytoplasmic OCT4 high group and combined Snail 1high / nuclear OCT4 high had significantly shorter OS (p <0.001, p= 0.003, 0.012, <0.001 and <0.001 respectively) and poor DFS (p< 0.001, p=0.001, 0.028, <0.001 and<0.001 respectively). Snail 1 was independent prognostic indicators for OS and DFS (P= 0.03 & p<0.001 respectively). Cytoplasmic OCT4 were independent prognostic factor for DFS (p= 0.035).
Conclusions:
1) Snail 1 is a marker of invasiveness and metastasis. Snail 1 is upregulated in IDC of the breast and can induce tumor cell metastasis in breast cancer. Snail1 expression is an independent negative predictor of prognosis in breast cancer
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2) OCT4 can be considered as a key regulator of tumor progression, aggressive behavior, and metastasis of IDC of the breast; therefore, OCT4 can be a potential marker for targeted therapy of IDC of the breast.
3) Our findings suggest that cytoplasmic and nuclear OCT4 may act co-operatively to regulate the progression of IDC of the breast and provide new insight into the function of OCT4 isoforms in carcinogenesis.
4) Our data indicated that OCT-4 and Snail 1 co-expression was associated with poor prognosis in breast cancer patients and co-expression of both markers may act cooperatively to promote tumor progression in breast cancer and may serve as biomarkers for predicting the outcome of breast cancer patients.