TK1 expression was found to be significantly different (P < 0.001) between normal breast and breast carcinoma tissue. A total of 73 breast carcinoma tissues (79%) were positive for TK1 expression while only 18 normal breast tissues (36%) scored positive. Breast tissue was also stained using an isotype control (mouse IgG, Upstate Company), and all breast tissue was found to be negative. Since these normal tissues were retrieved from the margins around a tumor and were considered pathologically normal, we sought to determine if tissue from noncancerous individuals yielded similar results. Interestingly, there was no TK1 staining in any breast tissue obtained from noncancerous individuals, called FDA-approved true normal tissue (data not shown). Therefore, these 18 TK1 positive normal tumor margins may not be false-positive results, but rather precarcinoma tissue, which is considered pathologically normal tissue by current standards. Further work is needed to better understand these potential differences.
TK1 expression was also found to be significantly different (P = 0.013) between the different types of breast carcinoma tissue. A chi-square test of independence was applied to compare the scores of the various types of breast carcinoma tissue. The Pearson chi-square value was 22.452, using 10 degrees of freedom, and the two-sided P-value was 0.013. The results are summarized in and typical staining can been seen in . In summary, infiltrating lobular carcinoma and scirrhous carcinoma tissues all stained positive for TK1, while 66–83% of simple, infiltrating duct, and medullary carcinoma tissues stained positive for TK1. Further studies with larger sample sizes may further elucidate the differences between these tissue types.
TK1 scoring of different types of carcinoma tissue.
Figure 1 TK1 breast tissue staining. (a) No TK1 staining was found in most normal duct tissue. TK1 positive staining could be found in the cytoplasm of tumor cells of (b) simple carcinoma, (c) infiltrating duct carcinoma, (d) medullary carcinoma, and (e) sclerosing (more ...)
In addition to the TK1 positive breast carcinoma tissues, 4 breast adenosis tissues (22%) were also found to be positive for TK1 expression. These 4 positive precancerous tissues were the first indication that TK1 expression may be an early event in tumor development. To pursue this hypothesis, we obtained a progressive breast array. This progressive breast array included tissue from different tumor developmental stages, such as normal, adenosis, and atypical hyperplasia, moderate atypical hyperplasia, severe hyperplasia, nonspecific infiltrating duct carcinoma, infiltrating lobular carcinoma, and infiltrating duct carcinoma with lymph node metastasis. The results are summarized in and typical staining can be seen in . The proliferating epithelial cells of some cases of breast adenosis were positive for TK1 expression as well as breast tissue with simple or atypical hyperplasia. As previously seen, most breast carcinoma tissues were also positive for TK1 expression while no breast tissue stained positive with an isotype control. It appears from this progressive array that since TK1 is found in precancerous tissue, TK1 upregulation is an early event in breast tumor development. These results support the previous conclusion that in some cases, there may be a difference between true normal tissue from noncancerous patients and the pathologically normal tumor margins. Further studies are needed to elucidate the differences between both the normal tumor margins and precancerous tissues that were positive for TK1 and those that were negative. Perhaps, the prognostic value of TK1 may be of help in identifying those precancerous tissues which are of greatest risk to the patient. Therefore, TK1 expression is an early event in tumor development and may aid in the identification of precancerous tissue.
TK1 scoring of breast progressive array.
Figure 2 Breast progressive array staining. (a) No TK1 staining was found in normal lobule breast tissue. However, TK1 staining was found in proliferating duct epithelial cells of precancerous tissue including, (b) breast adenosis, (c) breast adenosis with mild (more ...)