Molecular risk assessment for breast cancer development in patients with ductal hyperplasias.
OBJECTIVE
It has been reported that approximately a million women are diagnosed with benign breast lesions that include ductal hyperplasias per year in the United States. Recent studies that followed women with benign lesions have established that about 8% to 9% of them will subsequently develop invasive breast cancer (IBC). However, currently, there are no means of identifying a subclass of "true precancerous tissues" in women with ductal hyperplasias who will subsequently develop cancer. The purpose of this study is to investigate whether expression of hyaluronoglucosaminidase 1 (HYAL1), a known tumor promoter, in hyperplastic tissues identifies a "true precancerous stage" and predicts subsequent IBC development.


METHODS
A retrospective study was conducted with archival benign tissues of various histologic types and clinical information on development/nondevelopment of IBC. The control group was hyperplastic tissues from women who had no prior history of IBC and did not develop cancer in 5 to 7 years after diagnosis (n = 81). The test group was hyperplastic tissues from patients who developed cancer (n = 82). HYAL1 expression was studied by immunohistochemistry, and the results were statistically analyzed for significant association to develop cancer (P value), specificity, sensitivity, positive predictive value, and negative predictive value.


RESULTS
Statistical analysis of HYAL1 expression data showed very highly significant association between its expression and subsequent cancer development (P = 0) and very high sensitivity (0.83), specificity (0.84), positive predictive value (0.84), and negative predictive value (0.83).


CONCLUSIONS
The expression of HYAL1 in ductal hyperplastic tissues is a strong predictor of subsequent development of IBC; therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to screen benign tissues to predict subsequent development of IBC. Detection at the precancerous stage and treatment could drastically cut down breast cancer incidence and deaths from it.
Poola
Indira
I
Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, District of Columbia 20059, USA. ipoola@howard.edu
Abraham
Jessy
J
Marshalleck
Josephine J
JJ
Yue
Qingqi
Q
Lokeshwar
Vinatha B
VB
Bonney
George
G
Dewitty
Robert L
RL
D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis*; D006965:Hyperplasia; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000378:metabolism*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012189:Retrospective Studies; D018570:Risk Assessment
D014408:Biomarkers, Tumor; D006821:Hyaluronoglucosaminidase