Aberrant expression of E-cadherin in infiltrating ductal and lobular breast carcinomas and its correlation with clinicopathological parameters – A hospital-based study

Introduction: Breast carcinoma is one of the commonest malignant tumours in women, leading topremature deaths and morbidity. E-cadherin is a 120kDa calcium-dependent transmembraneglycoprotein encoded by the CDH1 gene located on chromosome 16q21 and is expressed in mostepithelial cells. Loss of E Cadherin expression implies cell discohesion and favours metastasis.Materials and Methods: A total of 30 cases of breast carcinomas were studied, over two years.Histological grade and type were assessed by staining the paraffin-embedded sections with H & E.Using IHC technique, E-cadherin antigen was retrieved by Heat-Induced Epitome Retrieval method,and immunostaining was scored semiquantitatively. Cases were grouped as ‘preserved,’ whenpositivity was strong membranous, and occurred in more than 75% of the neoplastic epithelial cellsand ‘aberrant’ in all the remaining cases. Results: E-cadherin was found to be preserved in 46.7%of all the breast carcinomas and aberrant in 51.7% of invasive ductal carcinomas (IDC) alone, while100% of invasive lobular carcinomas showed aberrant expression. No significant correlation wasfound with E-cadherin grading and histological type of carcinoma, histopathological grade orinvolvement of deep surgical margin. Conclusion: Differentiation between invasive ductal andinvasive lobular carcinoma based on the loss of E-cadherin has to be done cautiously given itsaberrant expression in ductal carcinomas as well.

Nottingham and the grade is now obtained by adding up the score for the tubule formation, nuclear pleomorphism, mitotic count. 10 The Nottingham modification of the Scarff-Bloom-Richardson (NSBR) grading system provides a platform for uniformity in grading [10,12]. The Nottingham Prognostic Index (NPI), is calculated from three parameters namely tumour size, lymph node stage and histologic grade [13]. It predicts prognosis and helps to distinguish groups of patients suitable for different forms of therapy [13].
The mechanism of progression is not completely recognised. Research suggests that the extracellular part of cadherin, via the ions of calcium, influences catenin with similar molecules on the neighbouring cell. Thus, they create an adhesive complex that maintains cells in compact connection [14]. The cancerous process results in the reduction of the amount of cadherin, which in turn results in disorder in the transition of intracellular signals, and loosened intercellular connections. This leads to increased cells' invasiveness and ability to migrate [15].
29 cases (97%) were women and one case (3%) was a 67-year-old man. 24 patients (80%) presented with breast lump alone, followed by breast lump associated with nipple retraction in 3 patients (10%), breast lump with nipple discharge in 2 patients (6.7%) and only one patient (3.3%) had breast lump associated with pain.
One case (3.3%) had a family history of carcinoma.
Concerning nuclear pleomorphism, eighteen cases (60%) had a score of 3, 12 (40%) has a score of 2 and none had a score of 1.

Thota S. et al: Aberrant expression of E-cadherin in infiltrating
The immunoreactivity with E-cadherin was scored semiquantitatively as follows: Strong

Discussion
In the present study, mean age was in concordance with the study conducted by Munjal. K et al. 27 and was lesser when compared to the other studies done by Amboise et al [28]. and Kowalski et al [26]. The mean age of Indian breast cancer patients is found to be lower when compared to the western countries with an average difference of 5 years. In the study conducted by Raina V et al. [29]. 7% of the carcinoma breast cases had a first degree relative with a history of breast cancer. In the present study, there is only one case of carcinoma breast with a family history, which accounts for 3.3%.In the current study, all the 30 cases (100%) presented with a breast lump, of which, 3 cases (10%) presented with associated nipple retraction, 2 cases (6.7%) with associated nipple discharge and one case (3.3%) presented with lump associated with pain. In the study conducted by Raina [29].In the study conducted by Ambroise et al. [28]. and Azizum -Nisa et al. [31]. the left breast was more commonly involved accounting for 59.2% and 57 % respectively. In the present study, an equal number of cases (15 cases, 50%) were seen involving the right and left breast. In the present study, most of the tumours ranged between 2-5cm, which correlated with the studies done by Ayadi L et al. [35]. and Muddawa et al. [22].The second commonest size was found to be < 2cm which correlated with Muddawa et al. [22]. The least number of cases showed tumour size of > 5cm which correlated with Ayadi et al. [35].
Found majority of lymph nodes status as negative (61.2%). While Kanithilatha et al. [23] found that 85.7% of IDC NOS showed preserved expression, Sauer et al. [39] found that only 15% showed preserved expression, neither of which is correlating with our study. However, 0% of ILC in our study shows preserved E-cadherin expression, which is comparable with all other studies (Table -12).