Tumor Biopsy

The diagnosis of malignant lymphomas is established by tumor biopsy sample, analysis of the biopsy tissue, and determination of the extent of the disease in the patient. 

Rojo F, Tabernero J, Albanell J, et al. Pharmacodynamic studies of gefitinib in tumor biopsy specimens from patients with advanced gastric carcinoma. J. Clin. Oncol. 2006 24 4309-4316. 

Based on these findings and toxicology studies [233], human clinical phase I studies have been initiated [234]. In tumor biopsies from melanoma patients obtained after treatment, a reduction was found in both the specific mRNA (M2 subunit of ribonucleotide reductase, RRM2) and in the protein (RRM2) levels when compared to pre-dosed tissue. The presence of an mRNA fragment that... 

Pathologic confirmation of lung cancer is established by examination of sputum cytology and/or tumor biopsy by bronchoscopy, mediastinoscopy, percutaneous needle biopsy, or open-lung biopsy. 

Noseda A, Berens ME, White JG, Modest EJ (1988) In vitro antiproliferative activity of combinations of ether lipid analogues and DNA interactive agents against human tumor cells. Cancer Res 48 1788-1791 Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259 1769-1771 O Brian CA, Vogel, VG, Singletary SE, Ward NE (1989a) Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 49 3215-3217... 

D invasion of microinjection-derived spheroids in collagen 3-D from 3-D Reproducible, automated, adaptable to other ECM components or fresh tumor biopsy material. 96-well system containing multiple spheroids/weU can be used in HT Specialist equipment needed, multiple spheroids/weU can potentially lead to secreted chemo-attractants (33)... 

O Brian C, Vogel VG, Singletary SE, et al. Elevated protein kinase C expression in human breast tumor biopsies relative to normal breast tissue. Cancer Res 1989 49(12) 3215-3217. 

The pathological response rate of chemo-RT compares favorably with that of any reported contemporary chemotherapy neo-adjuvant trial in this patient population (15-20). In addition, this study proved the feasibility of using biological correlates from pretreatment tumor biopsies to explore associations with pathological response. In fact, 11/21 patients (52%) with no evidence ofp53 overexpression at immunohistochemistry achieved a pathological response to the regimen, compared to 1/14 patients (7%) with overexpressed p53 (p = 0.010, Fisher exact text). 

The amount of DNA available from tissue samples, especially samples from tumor biopsies, is usually limited. Fortunately, whole-genome amplification has been developed to generate micrograms of DNA for further analysis (52,53). We found similar genotype calls and copy number changes in whole-genome amplified DNA with that using unamplified DNA, as determined by a 10 K SNP array analysis (30). 

At times there are very small amounts of tissue available for experimentation. Nevertheless, it is possible to isolate RNA from limited amounts of samples such as tumor biopsies or laser capture microdissected material [33], Although one can expect only small amounts of RNA from such tissues or cells, yields of RNA are enough for use in various applications, such as gene expression-related qualitative and quantitation studies using RT-PCR or even cDNA libraries [31,34], Small-scale RNA isolation is possible using commercially available kits that are available to isolate either total RNA or mRNA (Table 7.3). These kits can be used to isolate RNA from a few cells, or less than 1 mg of tissue. 

Traditional endoscopic and surgical procedures provide whole tumor samples well suited for microscopic examination and analysis in the pathology laboratory. The use of whole tissue tumor biopsies for proteomic studies has, however, raised several important issues that have been well demonstrated in CRC [9]. These include cellular heterogeneity in the different bowel parietal layers (mucosa, submucosa, muscularis mucosa, serosa) that may or may not be infiltrated, epithelial cell diversity in the mucosa itself, tissue infiltration by inflammatory cells such as lymphocytes, contamination with other body fluids, and protein degradation following tumor necrosis. In fact, epithelial cell content was found to vary between 9 and 67% in whole biopsies of normal mucosa and between 7 and 95% in tumor biopsies [10]. This study clearly demonstrates the likelihood of large cellular variation between tissue samples. 

Since tumor tissue is the primary manifestation of cancer, it contains the most immediate information and is the preferred material to investigate molecular targets. Experimental approaches will benefit from the enhanced protein concentration compared to body fluids. However, one major drawback of analyzing tumor biopsies is their limited availability and their heterogenicity which often requires microdissection. Alternatively, body fluids are the preferred clinical sources because they are most readily available in a noninvasive and continuous manner. 

Fig. 9.5. Implants for CAM assay. The sample (a) ean be a solid mass (e.g. tumor biopsy), or a solution trapped within a soUd substrate (natural or synthetic sponge, glass coversUde, nylon mesh/collagen sandwich). Solid samples are simply laid on the CAM in an avascular area (shown for the sponge implant). As an alternative, fluids can be injected directly into the aUantoic vesicle (b) so that their activity is extended to the whole vascular area.

Konno, K., Ishida, H., Hamashima, Y., Komatsuda, T., Sato, M., Furu-ya, T., Asanuma, Y., Masamune, O. Color Doppler findings of tumor seeding after US-guided liver tumor biopsy. Abdom. Imag. 1999 24 401-403... 

Analyses of the p53 status in tumor biopsies have revealed that patients with tumors with increased protein expression of p53 or a mutant p53 have a worse prognosis. This has been demonstrated for patients with bladder, breast, colon, gastric, nonsmall cell lung, oesophagus, ovarian and prostate carcinoma and the group of soft-tissue sarcomas (11,21-37). 

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