Expression of MHC class II-associated invariant chain (Ii; CD74) in invasive breast carcinoma: Its relation to Nottingham prognostic index, hormone-receptors' & Her-2 immunoprofile

Author(s):  
Eiman Adel Hasby Saad
2016 ◽  
Vol 103 (2) ◽  
pp. 193-203
Author(s):  
Eiman Adel Hasby ◽  
Rana Adel Khalifa

Purpose To study the immunohistochemical expression of CD74 in series of invasive breast carcinomas classified according to their estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunoprofile and explore its correlation to Nottingham Prognostic Index (NPI) and tumor pathologic stage to determine if it has a prognostic value. Methods A total of 160 cases of mammary carcinoma were classified broadly according to their ER, PR, and HER2 expression into luminal, HER2-positive, and triple-negative groups. The NPI was calculated and pathologic stage was recorded for each individual case and cases were classified into different prognostic groups. The CD74 expression was evaluated immunohistochemically and correlated to different prognostic variables. Results The CD74 immunohistochemical expression in invasive breast carcinoma was significantly higher in triple-negative tumors, higher tumor grades, presence of lymph nodal metastasis, higher tumor stages, and higher NPI scores. Conclusions The CD74 might be a useful prognostic indicator predicting poor outcome of patients with breast carcinoma. Its consistent expression in triple-negative breast carcinomas points to the need of further studies to test the possibility if it can be targeted in treatment of breast carcinoma, especially in such groups.


2010 ◽  
Vol 123 (21) ◽  
pp. 3817-3827 ◽  
Author(s):  
W. Zwart ◽  
V. Peperzak ◽  
E. de Vries ◽  
A. M. Keller ◽  
G. van der Horst ◽  
...  

1993 ◽  
Vol 177 (3) ◽  
pp. 583-596 ◽  
Author(s):  
P Romagnoli ◽  
C Layet ◽  
J Yewdell ◽  
O Bakke ◽  
R N Germain

Invariant chain (Ii), which associates with major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum, contains a targeting signal for transport to intracellular vesicles in the endocytic pathway. The characteristics of the target vesicles and the relationship between Ii structure and class II localization in distinct endosomal subcompartments have not been well defined. We demonstrate here that in transiently transfected COS cells expressing high levels of the p31 or p41 forms of Ii, uncleaved Ii is transported to and accumulates in transferrin-accessible (early) endosomes. Coexpressed MHC class II is also found in this same compartment. These early endosomes show altered morphology and a slower rate of content movement to later parts of the endocytic pathway. At more moderate levels of Ii expression, or after removal of a highly conserved region in the cytoplasmic tail of Ii, coexpressed class II molecules are found primarily in vesicles with the characteristics of late endosomes/prelysosomes. The Ii chains in these late endocytic vesicles have undergone proteolytic cleavage in the lumenal region postulated to control MHC class II peptide binding. These data indicate that the association of class II with Ii results in initial movement to early endosomes. At high levels of Ii expression, egress to later endocytic compartments is delayed and class II-Ii complexes accumulate together with endocytosed material. At lower levels of Ii expression, class II-Ii complexes are found primarily in late endosomes/prelysosomes. These data provide evidence that the route of class II transport to the site of antigen processing and loading involves movement through early endosomes to late endosomes/prelysosomes. Our results also reveal an unexpected ability of intact Ii to modify the structure and function of the early endosomal compartment, which may play a role in regulating this processing pathway.


2017 ◽  
Vol 7 (1) ◽  
pp. 1078-1083
Author(s):  
A Pradhan ◽  
P Paudyal ◽  
AK Sinha ◽  
CS Agrawal

Background: Breast carcinoma is the most frequent malignant tumor in women accounting for approximately 15% of female cancer deaths. It is the second most common malignancy among women in Nepal. Our objectives were to study the extent and spread of different histological types breast carcinoma in the eastern region of Nepal, to grade and stage the tumors, score the prognosis.Materials and Methods: A cross-sectional descriptive study of mastectomy specimens with axillary lymph node sampling was done for a period of two years. Diagnosis was done using WHO classification. Modified Bloom Richardson score and TNM system was used to grade and stage the tumors. Nottingham Prognostic index was applied to score the prognosis.Results: Out of 31 total cases, the most common histologic type was Invasive Carcinoma of No Special Type (67.74%). The largest tumor size was of 12cm which had poor NPI score. Most tumors were of grade II and T2. Out of 30 cases with lymph nodes, 13 were negative for metastasis pN0, 10 were pN1 and 7 were pN2. Extranodal spread was observed in 6 out of 17 cases with lymph node metastasis and was associated with higher grades and poor prognosis.Conclusion: Higher grade tumors, lymph node metastasis and extranodal extension are associated with higher Nottingham Prognostic Index score. 


1993 ◽  
Vol 177 (6) ◽  
pp. 1699-1712 ◽  
Author(s):  
E K Bikoff ◽  
L Y Huang ◽  
V Episkopou ◽  
J van Meerwijk ◽  
R N Germain ◽  
...  

We used gene targeting techniques to produce mice lacking the invariant chain associated with major histocompatibility complex (MHC) class II molecules. Cells from these mice show a dramatic reduction in surface class II, resulting from both defective association of class II alpha and beta chains and markedly decreased post-Golgi transport. The few class II alpha/beta heterodimers reaching the cell surface behave as if empty or occupied by an easily displaced peptide, and display a distinct structure. Mutant spleen cells are defective in their ability to present intact protein antigens, but stimulate enhanced responses in the presence of peptides. These mutant mice have greatly reduced numbers of thymic and peripheral CD4+ T cells. Overall, this striking phenotype establishes that the invariant chain plays a critical role in regulating MHC class II expression and function in the intact animal.


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