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Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

Caballero OL, Shousha S, Zhao Q, Simpson AJ, Coombes RC, Neville AM - Oncoscience (2013)

Bottom Line: We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas.In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast.ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Collaborative Laboratory, Ludwig Institute for Cancer Research, Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD USA.

ABSTRACT
Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry staining of DCIS samples using monoclonal antibody specific to MAGEA (clone 6C1) (shown in brown)Sections presented variable cytoplasmic MAGEA staining, typically showing either focal and scattered positive cells (A and B) or intense and diffuse positivity (C) in >90% of tumor cells. Original magnification, ×200.
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Figure 2: Immunohistochemistry staining of DCIS samples using monoclonal antibody specific to MAGEA (clone 6C1) (shown in brown)Sections presented variable cytoplasmic MAGEA staining, typically showing either focal and scattered positive cells (A and B) or intense and diffuse positivity (C) in >90% of tumor cells. Original magnification, ×200.

Mentions: Based on the encouraging RNA expression results, we decided to analyze further the expression of CT antigens by IHC using previously characterized antibodies specific to MAGEA and NY-ESO-1 in the same samples (Table 1). Adequate antibodies were not available for analyzing the expression of the remaining CT proteins investigated in this study. Similar to the results of the RT-PCR, NY-ESO-1 protein expression was detected not only in DCIS but also in benign proliferative lesions whereas areas of normal breast were always negative for NY-ESO-1 expression (in 19/23 or 82.6% of DCIS; and in 7/12 or 58.3% of benign proliferative lesions), but it was not detected any LCIS tested. In some cases, NY-ESO-1 was found to be diffusely and homogenously detected in almost all tumor cells (Figure 1A, B and C) and in others, NY-ESO-1 expression was heterogeneous. Some cases showed patchy expression, whilst others showed only small clusters of tumor cells with strong expression within a background of CT-negative tumor cells (Figure 1D). NY-ESO-1 was more frequently detected in the nuclei but combined nuclear and cytoplasmic or purely cytoplasmic staining was also observed (Figure 1). RT-PCR and IHC results were concordant in 56.4% of the cases. Six cases (15.4%) were negative by IHC but positive by RT-PCR, which could be explained by the lower sensitivity of IHC versus RT-PCR. Conversely, 11 cases (28.2%) were positive by IHC but negative by RT-PCR. A possible reason for this is mRNA degradation due to the formalin fixation process and contamination with RNAses or because only a small cluster of tumor cells with strong expression was seen amongst a background of CT-negative tumor and normal cells within the section. MAGEA protein was observed in three DCIS cases, the same cases where MAGEA3 mRNA expression was detected. Similarly to NY-ESO-1, and except for one case, the positivity was observed in a small cluster of tumor cells with strong expression amongst a background of CT-negative tumor cells (Figure 2).


Expression of Cancer/Testis genes in ductal carcinoma in situ and benign lesions of the breast.

Caballero OL, Shousha S, Zhao Q, Simpson AJ, Coombes RC, Neville AM - Oncoscience (2013)

Immunohistochemistry staining of DCIS samples using monoclonal antibody specific to MAGEA (clone 6C1) (shown in brown)Sections presented variable cytoplasmic MAGEA staining, typically showing either focal and scattered positive cells (A and B) or intense and diffuse positivity (C) in >90% of tumor cells. Original magnification, ×200.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295763&req=5

Figure 2: Immunohistochemistry staining of DCIS samples using monoclonal antibody specific to MAGEA (clone 6C1) (shown in brown)Sections presented variable cytoplasmic MAGEA staining, typically showing either focal and scattered positive cells (A and B) or intense and diffuse positivity (C) in >90% of tumor cells. Original magnification, ×200.
Mentions: Based on the encouraging RNA expression results, we decided to analyze further the expression of CT antigens by IHC using previously characterized antibodies specific to MAGEA and NY-ESO-1 in the same samples (Table 1). Adequate antibodies were not available for analyzing the expression of the remaining CT proteins investigated in this study. Similar to the results of the RT-PCR, NY-ESO-1 protein expression was detected not only in DCIS but also in benign proliferative lesions whereas areas of normal breast were always negative for NY-ESO-1 expression (in 19/23 or 82.6% of DCIS; and in 7/12 or 58.3% of benign proliferative lesions), but it was not detected any LCIS tested. In some cases, NY-ESO-1 was found to be diffusely and homogenously detected in almost all tumor cells (Figure 1A, B and C) and in others, NY-ESO-1 expression was heterogeneous. Some cases showed patchy expression, whilst others showed only small clusters of tumor cells with strong expression within a background of CT-negative tumor cells (Figure 1D). NY-ESO-1 was more frequently detected in the nuclei but combined nuclear and cytoplasmic or purely cytoplasmic staining was also observed (Figure 1). RT-PCR and IHC results were concordant in 56.4% of the cases. Six cases (15.4%) were negative by IHC but positive by RT-PCR, which could be explained by the lower sensitivity of IHC versus RT-PCR. Conversely, 11 cases (28.2%) were positive by IHC but negative by RT-PCR. A possible reason for this is mRNA degradation due to the formalin fixation process and contamination with RNAses or because only a small cluster of tumor cells with strong expression was seen amongst a background of CT-negative tumor and normal cells within the section. MAGEA protein was observed in three DCIS cases, the same cases where MAGEA3 mRNA expression was detected. Similarly to NY-ESO-1, and except for one case, the positivity was observed in a small cluster of tumor cells with strong expression amongst a background of CT-negative tumor cells (Figure 2).

Bottom Line: We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas.In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast.ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

View Article: PubMed Central - PubMed

Affiliation: Ludwig Collaborative Laboratory, Ludwig Institute for Cancer Research, Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD USA.

ABSTRACT
Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

No MeSH data available.


Related in: MedlinePlus