Prognostic relevance of aberrations in the erbB oncogenes from breast, ovarian, oral and lung cancers: Double-differential polymerase chain reaction (ddPCR) for clinical diagnosis

• Published in: Gene Vol. 159; no. 1; pp. 35 - 42
• Main Authors: Brandt, B., Vogt, U., Schlotter, C.M., Jackisch, C., Werkmeister, R., Thomas, M., von Eiff, M., Bosse, U., Assmann, G., Zänker, K.S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 14-06-1995
• Subjects: average gene copy number; Base Sequence; Breast Neoplasms - chemistry; Breast Neoplasms - diagnosis; Breast Neoplasms - genetics; Breast Neoplasms - mortality; Breast Neoplasms - pathology; DFS; Disease-Free Survival; DNA, Neoplasm - analysis; Female; Gene Dosage; Genes, erbB - genetics; Humans; local recurrence; Lung Neoplasms - chemistry; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Metastasis; Molecular Sequence Data; Mouth Neoplasms - chemistry; Mouth Neoplasms - diagnosis; Mouth Neoplasms - genetics; Neoplasm Metastasis; Ovarian Neoplasms - chemistry; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Polymerase Chain Reaction - methods; Prognosis; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; tyrosine kinase receptors; T, tumor size; erbB-2 3,4), encoding c-erbB-2 (3,4) oncoprotein; PgR, progesteron receptor; HBB, gene encoding β-globin; Metastasis; ER, estrogen receptor; NSCLC, non-small-cell lung cancer; DFS; tyrosine kinase receptors; average gene copy number; local recurrence; Mb, megabase(s) or 10 6 bp; EGF-R, epidermal growth factor receptor; p.op., post operative; mo, month(s); erbB-1, gene encoding EGF-R; DCIS, ductal carcinoma in situ; ddPCR, double-differential PCR; N, nodal status; OS, overall survival; RR, relative risk; AGCN, average gene copy number(s); d k, critical difference (of AGCN values, means the analytical sensitivity of the method); RFLP, restriction-fragment-length polymorphism; M, distant metastasis at time of primary treatment; DFS, disease-free survival
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/0378-1119(94)00652-9

We have determined the average gene copy numbers (AGCN) of the
erbB-1 gene, encoding the epidermal growth factor receptor (EGF-R), the
erbB-2 and the
erbB-3 genes in breast, ovarian, oral, and lung cancer tissue by using double-differential PCR (ddPCR). The ddPCR method comprises the co-amplification of the single-copy gene
HBB, the
erbB-1, erbB-2 and
erbB-3 oncogenes and the second single-copy reference gene
SOD2 under equal reaction conditions. In a retrospective study the AGCN of the
erbB genes and the time up to the appearance of metastases were subjected to life-table analysis in 128 women with primary breast cancer. Patients whose breast cancer tissue showed an AGCN for
erbB-1 of less than 0.4 and greater then 1.6, as expected from the literature, for
erbB-2 of greater than 2.0 and for
erbB-3 of less than 1.75 had decreased disease-free survival (DFS). The quotient of
erbB-1 and
erbB-2 AGCN was the most significant in multivariate Cox analysis followed by nodal status and progesterone receptor status. In extensive studies a similar association between
erbB AGCN and metastasis was seen in ovarian cancer and oral cancer, though
erbB oncogene aberrations in those entities were not as frequent as in breast cancer. The AGCN of
erbB oncogenes may not be of prognostic value in untreated lung cancer patients.