New cutpoints to identify increased HER2 copy number: analysis of a large, population-based cohort with long-term follow-up.

BACKGROUND: HER2 gene amplification and/or protein overexpression in breast cancer is associated with a poor prognosis and predicts response to anti-HER2 therapy. We examine the natural history of breast cancers in relationship to increased HER2 copy numbers in a large population-based study. PATIENTS AND METHODS: HER2 status was measured by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in approximately 1,400 breast cancer cases with greater than 15 years of follow-up. Protein expression was evaluated with two different commercially-available antibodies. RESULTS: We looked for subgroups of breast cancer with different clinical outcomes, based on HER2 FISH amplification ratio. The current HER2 ratio cut point for classifying HER2 positive and negative cases is 2.2. However, we found an increased risk of disease-specific death associated with FISH ratios of >1.5. An 'intermediate' group of cases with HER2 ratios between 1.5 and 2.2 was found to have a significantly better outcome than the conventional 'amplified' group (HER2 ratio >2.2) but a significantly worse outcome than groups with FISH ratios less than 1.5. CONCLUSION: Breast cancers with increased HER2 copy numbers (low level HER2 amplification), below the currently accepted positive threshold ratio of 2.2, showed a distinct, intermediate outcome when compared to HER2 unamplified tumors and tumors with HER2 ratios greater than 2.2. These findings suggest that a new cut point to determine HER2 positivity, at a ratio of 1.5 (well below the current recommended cut point of 2.2), should be evaluated.

[Formalized macroscopic description and computer analyser of macroscopic image (as illustrated by gastric pathology)]. / Formalizovannoe makroskopicheskoe opisanie i komp'iuternyi analizator makroskopicheskogo izobrazheniia (na primere issledovaniia patolodii zheludka).

A computer analyzer is regularly used in the department of pathology in formalized macrodescription of the stomach. Advantages of this method are described.

[Deletion of YNZ22 and ALU-VPA/MYCL1 loci in human colonic adenocarcinoma and postoperative prognosis]. / Deletsii lokusov YNZ22 i ALU-VPA/MYCL1 v adenokartsionomakh tolstoi kishki cheloveka i posleoperatsionnyi prognoz.

Since deletions of the short arm of chromosome 17 are the most common genetic defects in human colorectal carcinoma (CC), we tested the YNZ22 locus (D17S30, 17p13.3) for loss of heterozygosity (LH) in adenocarcinoma and in the normal colonic mucosa of 49 CC patients, and studied the association of LH with clinicomorphological features of the tumor. Allele frequency distribution of YNZ22 did not differ for the patients and healthy people. LH in YNZ22 in the tumor was found in 33% (13/39) of all informative cases, its frequency being thrice higher in men than in women (chi 2 = 5.21, p = 0.022). The defect was associated with moderate or poor histological differentiation (P2 = 0.0055) and polyploidy > 3n (P2 = 0.0035) of tumor cells and with high incidence of post-surgery relapse or metastasis. Analysis of both YNZ22 and Alu-VpA/MycL1 (1p34.3) loci in the tumor allowed reliable relapse prognosis in 76% of the CC patients. The probability of post-surgery relapse or metastasis was estimated at no less than 67% for patients with LH in at least one of the two loci in the tumor, and at somewhat more than 20% for patients without LH.

[Statistical analysis in the assessment of diagnostic and prognostic significance of nucleolus organizer regions in colorectal epithelial neoplasms]. / Statisticheskii analiz pri otsenke diagnosticheskoi i prognosticheskoi znachimosti oblastei iadryshkovykh organizatorov v épitelial'nykh opukholiakh tolstoi kishki.

Different parametric and non-parametric methods of statistics have been analysed in the assessment of diagnostic and prognostic value of nucleolar organizer regions (NORs) in epithelial colorectal neoplasms. NORs activity was studied in adenomas and so-called "small" adenocarcinomas invading only mucosa and submucosa. The data obtained show that NORs activity can help in the differential diagnosis of adenomas and in situ adenocarcinomas of the colorectum. Results of NORs evaluation depend primarily on the statistical methods used.

[Metachronous cancer of the gastro-intestinal tract with signs of endocrine-cell differentiation]. / Metakhronnyi rak zheludochno-kishechnogo trakta s priznakami éndokrinnokletochnoi differentsirovki.

A case of metachronous cancer of gastrointestinal tract is reported. Three poorly differentiated malignant epithelial tumours developed in a 27-year-old patient within three years. They located in the stomach, small and large intestine. Light-microscopically, the tumours were formed mainly of non-differentiated rounded cells with occasional signet ring cells. At electron microscopic examination the presence of mucin granules was confirmed. Moreover, a variable amount of electron-dense endocrine-like granules was found in tumour cells. According to some publications, endocrine differentiation of gastrointestinal cancers is considered to be a poor prognostic feature, hence electron microscopy or special staining when possible can be important in the evaluation of prognosis.

[Geographic differences in the frequency of chromosome alterations characteristic of cancer of the large intestine]. / Geograficheskie razlichiia v chastote khromosomnykh izmenenii kharakternykh dlia raka tolstoi kishki.

The authors' material (33 tumours) and that from foreign literature (18 to 100 tumours from every country) was used. The following chromosome aberrations were compared: the deletion of a part of chromosome 1 short arm, deletion of chromosome 5 and a part of its long arm, additional chromosomes 7, complete or partial deletion of chromosome 17 short arm, deletion of chromosome 18 and appearance of additional chromosomes 20. Clear-cut differences were revealed between the following three groups of regions: 1) countries of the Eastern and Western Europe (Russia, France, Germany); 2) Northern Europe countries (Denmark, SWeden); 3) USA and China. Geographical differences in chromosome anomalies in hemoblastosis were found in 1970s, the difference in colon carcinoma are presented for the first time. The experimental results suggest that non-homogeneous distribution of the karyotype alterations typical for certain morphological types of malignant tumours are due to different environmental influences.