https://www.hal.inserm.fr/inserm-00561753/document

International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society International Multidisciplinary Classification of Lung Adenocarcinoma

Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes.

A pathology atlas of the human cancer transcriptome

https://www.cell.com/cell/pdf/S0092-8674(05)00342-9.pdf

Identification of Bronchioalveolar Stem Cells in Normal Lung and Lung Cancer

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines

Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a “Janus face” in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O2 sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1α, GLUT-1, CA IX) or exogenous bioreductive drugs. In many—albeit not in all—studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.

Hypoxia in cancer: significance and impact on clinical outcome

BACKGROUND

Increased expression of Glut1 and Glut3 has been reported in many human cancers, including nonsmall cell lung carcinoma (NSCLC). The aim of this study was to determine the biologic significance of Glut1 and Glut3 overexpression in Stage I NSCLC.



METHODS

Using immunohistochemistry and polyclonal anti-Glut1 and anti-Glut3 antibodies, the authors immunostained sections of formalin fixed, paraffin embedded tissues from 289 Stage I NSCLCs. The Kaplan-Meier survival method, the log rank test, and Fisher's exact test were used for statistical analysis.



RESULTS

Of the 289 cases, 49 (17%) were negative for both Glut1 and Glut3, 239 (83%) were Glut1 positive, 61 (21%) were Glut3 positive, 179 (62%) were positive for Glut1 but negative for Glut3, 1 (0.3%) was positive for Glut3 but negative for Glut1, and 60 (21%) were positive for both Glut1 and Glut3. Only 1 of 50 Glut1 negative tumors (2%) was positive for Glut3, whereas 60 of 239 Glut1 positive tumors (25%) were positive for Glut3 (P < 0.0001). Glut1 or Glut3 were detected more often in poorly differentiated and undifferentiated tumors (P <0.0001 and P = 0.0008, respectively). Overexpression of Glut1 and/or Glut3 was associated with poorer survival (P = 0.0133), especially in patients with well-differentiated and moderately differentiated tumors (P = 0.0017).



CONCLUSIONS

In Stage I NSCLC, Glut3 overexpression likely occurs after Glut1 overexpression. The appearance of Glut1 positive clones is associated with aggressive biologic behavior, which is worsened by the emergence of Glut3 positive clones. Glut1 and Glut3 are significant of poor prognosis indicators in cases of NSCLC. Cancer 1997; 80:1046-51. © 1997 American Cancer Society.

Overexpression of glut1 and glut3 in stage I nonsmall cell lung carcinoma is Associated with poor survival

Retinoblastoma (RB) protein expression was examined in paraffin and frozen tissue sections of 36 primary non-small cell lung carcinomas (NSCLC) using immunohistochemistry with confirmation by direct Western blotting. A normal RB protein staining pattern was present in 24 and absent in 10 NSCLC. Two additional RB positive primary tumors have major foci in which all tumor cells showed no RB protein staining. Significantly more high-stage (stages III and IV) NSCLC had altered RB protein expression than those with low-stage (stages I and II) tumors ( P < 0.05). The results suggest that absence of the RB expression may be associated with the initiation and/or progression of many NSCLC. This is the first report of successful RB staining in paraffin sections.

https://cancerres.aacrjournals.org/content/canres/51/10/2735.full.pdf

Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas.

The diagnostic utility of several antibodies against desmin and their optimal staining conditions have not been systematically evaluated. Sections of paraffin-embedded tissues from 584 cases were stained with a monoclonal antibody against desmin (Clone DER 11 ® from DAKO), using an avidin-biotin-peroxidase technique. The results were tabulated and compared with those from previous reports. The following observations were made: (1) When pronase digestion was performed before staining, desmin was equally demonstrable in tissues fixed in formalin, Zenker's, Bourn's, or B5 fixative; however, desmin staining was lost or significantly diminished in tissues fixed in absolute ethyl alcohol. In contrast, when pronase was not used, a positive staining was demonstrated only in tissue fixed in absolute ethyl alcohol. (2) Positive staining was found in normal muscle (92 of 92 cases), leiomyoma (12 of 13), rhabdomyoma (6 of 6), rhabdomyosarcoma (31 of 31), leiomyosarcoma (18 of 26). (3) Desmin was never found in epithelia, normal mesenchymal tissue other than muscle, tumors simulating rhabdomyosarcoma, and epithelial tumors. (4) A positive staining was documented in 1 tumor (a fibrous histiocytoma) of 42 benign predominantly spindle cell tumors and in 8 of 89 predominantly spindle cell sarcomas. (5) Desmin was never documented in myoepithelial cells but stained myofibroblasts in 2 of 12 examples of granulation tissue and in 29 of 67 samples containing tumor-associated desmoplasia. The authors1 data on the diagnostic sensitivity and specificity of the evaluated antibody should improve the use of desmin in diagnostic pathology.

The diagnostic utility of desmin. A study of 584 cases and review of the literature.

Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.

Philip T. Cagle

Papers

Overexpression of glut1 and glut3 in stage I nonsmall cell lung carcinoma is Associated with poor survival

Absence of retinoblastoma protein expression in primary non-small cell lung carcinomas.

The diagnostic utility of desmin. A study of 584 cases and review of the literature.

Localized malignant mesothelioma.

Postpneumonectomy compensatory lung growth.