Detection of amplified int-2/FGF-3 gene in primary breast carcinomas using differential polymerase chain reaction

Amplification of int-2/FGF-3 gene was investigated by differential polymerase chain reaction (dPCR) in 440 archival primary breast carcinoma tissues. Of these, 23 were comedo ductal carcinoma in situ (DCIS), 18 were non-comedo DCIS, 41 were comedo DCIS with adjacent invasive ductal carcinomas, 19 were non-comedo DCIS with adjacent invasive ductal carcinomas, 270 were invasive ductal carcinomas, 33 were invasive lobular carcinomas, 21 were colloid carcinomas and 15 were medullary carcinomas. Int-2 was amplified in 22% (96/440) of the primary breast carcinomas. It was shown that int-2 was amplified in 13% (3/23) of the comedo DCIS, 17% (7/41) of the comedo DCIS and 29% (12/41) of the adjacent invasive ductal carcinomas, 26% (71/270) of the invasive ductal carcinomas, 18% (6/33) of the invasive lobular carcinomas, 10% (2/21) of the colloid carcinomas and 13% (2/15) of the medullary carcinomas. In contrast, int-2 was not amplified in non-comedo DCIS and invasive ductal carcinomas with adjacent non-comedo DCIS lesions. A significant association was observed between int-2 amplification in the in situ components and adjacent invasive lesion (P<0.05). All tumors with int-2 amplification in the in situ lesions (7/7) also demonstrated same degree of amplification in the adjacent invasive components. However, 9% (5/53) of the tumors with no amplified int-2 gene in the in situ components showed int-2 amplification in the adjacent invasive lesions. A significant relationship was noted between amplification of int-2 and lymph node metastases (P<0.05) and poorly differentiated tumors (P<0.05) but not with estrogen receptor status (P>0.05) and proliferation index (Ki-67 and PCNA) (P>0.05). In Malaysia, majority of the patients belong to younger age group (<50 years old) but a comparison of the age groups showed that the amplification of int-2 was not statistically associated with patient age (P>0.05). These observations indicate that amplification of int-2 tends to strengthen the view that int-2 may have the potential to be an indicator of poor prognosis regardless of the age of the patient. Moreover, the presence of int-2 amplification in preinvasive, preinvasive and adjacent invasive lesions, and invasive carcinomas suggest that int-2 could be a marker of genetic instability occurring in early and late stages of tumor development.