Telomerase activity in human breast cancer and benign breast lesions: Diagnostic applications in clinical specimens, including fine needle aspirates

Abstract

We analysed telomerase activity in normal, benign and malignant breast tissues and in fine needle aspirates by a PCR-based assay. The tissue samples we used in this assay consisted of 20 cryostat sections, I0 pm thick, from each breast biopsy. This method was used to obtain effective extraction from small samples and to confirm the histological identity of the specimen by microscopical examination of serial sections. Fifty-two of 7 I breast carcinomas were positive for telomerase activity, and the intensity of this was strong in most cases, whereas all 6 samples of normal breast tissue and 17 of fibrocystic disease were negative and only I of I 5 fibroadenomas was positive. lnvasive ductal carcinomas were more frequently positive than invasive lobular carcinomas. There was no correlation of telomerase activity with turnour size or the occurrence of lymph node metastasis. Evaluation of our assay system showed that a signal of telomerase activity was detectable in extracts from single cryostat sections (< I mm2) of a cancer specimen and from as few as 4 cells of a human breast cancer cell line. On the basis of the above data, we applied this assay to fine needle aspirates of breast lesions. Ten of 15 aspirates which had been cytopathologically diagnosed as cancer were strongly positive, while 26 of 29 benign aspirates were totally negative and the remaining 3 showed only borderline activity. In 3 cases, the telomerase result could have helped establish a diagnosis when the cytological observations were inconclusive. Our results indicate that this sensitive assay could become a useful new modality for supplementing microscopic cytopathology in the detection of cancer cells in small tissue biopsies and fine needle aspirates.o 1996 Wiley-Liss, Inc.

Detection of telomerase activity in exfoliated cancer cells in colonic luminal washings and its related clinical implications

“…Following the development by Kim et al (1994) of an extremely sensitive PCR-based assay, telomerase activity has been found in a large variety of solid tumours, including neuroblastomas (Hiyama et al, 1995a), lung carcinomas (Hiyama et al, 1995b), hepatomas (Tahara et al, 1995a), gastric and colon carcinomas (Chadeneau et al, 1995;Hiyama et al, 1995c;Tahara et al, 1995bLi et al, 1996, breast carcinomas (Hiyama et al, 1996;Sugino et al, 1996) and brain tumours (Langford et al, 1995). In the present study, the activity of this enzyme was demonstrated in more than 90% of colorectal carcinomas in line with previous studies (Chadeneau et al, 1995;Tahara et al, 1995b;Li et al, 1996).…”

Telomerase activity in ductal carcinoma in situ and invasive breast cancer

“…More recently, some studies have found correlations between telomerase activity and stage, traditional prognostic indicators, and clinical outcome in invasive breast cancer (Clark et al, 1997;Hoos et al, 1998). Other studies, however, failed to show a correlation between telomerase activity and prognostic factors or clinical outcome in breast cancer (Bednarek et al, 1997;Carey et al, 1998;Nawaz et al, 1997;Sugino et al, 1996;Tsao et al, 1997) and (Carey et al, in preparation, 1999).…”

Telomere and telomerase in oncology

“…In our experiment, we have identified the telomerase activity in 293 cells and several human liver carcinoma cells respectively by telomerase TRAP-ELISA assay and non-radioisotopic silver staining telomeric repeat amplification protocol [24], [25]. The high sensitivity of the PCR-based TRAP assay has allowed the analysis of minimal tissue samples, such as fineneedle aspirates of the liver, breast and thyroid, cervical smears, oral washings, and urine [26][27][28][29][30][31]. In some experiments the sensitivity and specificity of the assay in detecting tumor cells has been compared with the gold standard, that is, cytology.…”