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A suitable treatment method for this triple-negative breast cancer has not yet been developed, and compared with breast cancer cases in which any of the existing 3 markers are positive, the prognosis of its patients is not good (refer to non-patent documents 9 and 10 )
[0007] In addition, among intraductal breast tumors, malignant non-invasive ductal carcinoma in situ (ductal carcinoma in situ; hereinafter also referred to as DCIS) and benign intraductal papilloma (intraductal papilloma) For the identification of tumors, the previous histopathological diagnosis method using HE (hematoxylin, eosin) stained specimens was carried out. However, the definite identification elements are not clear, and many lesions are difficult to identify.
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[0109] Hereinafter, the present invention will be described more specifically through examples, but the present invention is not limited to any limitation of the examples.
reference example 1
[0110] The selection of reference example 1 experimental sample
[0111] The inventor randomly selected 10 cases of intraductal papilloma (intraductal papilloma) and 10 cases of non-invasive breast ductal carcinoma (DCIS) from breast neoplastic lesions that were surgically resected in the affiliated institution from 2005 to 2009. Pathological specimens of 87 surgical materials in total and 67 cases of invasive carcinoma. Among them, there were 17 cases of triple-negative invasive cancer that were negative for ER, PgR, and HER2.
Embodiment 1
[0112] Example 1 Staining using anti-LAT antibody
[0113] Make 10% formalin-fixed paraffin-embedded blocks for all breast neoplastic lesions selected in Reference Example 1, and then make 3 μm thin slices from the representative block with the largest proportion of the neoplastic lesions, and microwave for 5 minutes. After surviving, the mouse anti-LAT1 monoclonal antibody prepared by the present inventors (referring to page 23631 of Non-Patent Document 1) image 3 A) React overnight at a temperature below 4°C. Add the general-purpose antibody of DAKO ChemMate ENVISION System HRP Kit, let it react at room temperature for 30 minutes, and develop the color with DAB (3,3'-diaminobenzidine tetrahydrochloride) substrate solution. For nuclear staining, methyl green or Mayer's hematoxylin staining was performed. Ventana XT system (Ventana Japan, Tokyo, Japan) was used for immunostaining of ER and PgR, and immunostaining of HER2 was performed by DAKO EGFR pharmDx kit (Dako North Am...
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Abstract
[Problem] To provide a marker which serves as a measure for the treatment of breast cancer. [Solution] A kit for the diagnosis of breast cancer, which comprises an anti-LAT1 monoclonal antibody and / or a method for diagnosing breast cancer using an anti-LAT1 monoclonal antibody. Among mammary gland neoplastic lesions, ductal carcinoma in situ, which is malignant, undergoes the expression of LAT1 at a significantly high level compared with intraductal breast papilloma, which is benign. Therefore, an anti-LAT1 monoclonal antibody is useful for the discrimination between the two lesions. Further, LAT1 is expressed at a high level in most of triple-negative infiltrating carcinomas which are negative for all of ER, PgR and HER2 that are conventional molecular targeting markers for breast cancer and for which there is no proper molecular targeted therapy method. Therefore, LAT1 can be used as a novel molecular targeting marker for breast cancer. The expression of LAT1 can be diagnosed by the present immunohistological method, and the development of a molecular targeted therapy method in which LAT1 is targeted is effective.
Description
technical field [0001] The present invention relates to a biomarker of breast cancer, and more specifically relates to a diagnostic kit and a diagnostic method for breast tumors. Background technique [0002] Neutral amino acid transporter (L-type amino acid transporter, L-type amino acid transporter (LAT)) is used for glycine, alanine, leucine, isoleucine, valine, serine, threonine , cysteine, asparagine, glutamine, methionine, phenylalanine, tyrosine, tryptophan, histidine, levodopa and other neutral amino acids uptake into cells transmembrane protein . The present inventors conducted studies on various LATs, and so far discovered LAT1 and LAT2, LAT3, and LAT4 which are isoforms thereof. [0003] Among them, LAT1 is a large medium-sized medium with leucine, isoleucine, valine, methionine, phenylalanine, tyrosine, tryptophan, and histidine through the coexistence of the amino acid transport active factor 4F2hc. Sexual amino acids and levodopa Na + A 12-transmembrane pro...
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