Computer-Assisted Analysis of Biopsy Specimen Microvessels Predicts the Outcome of Esophageal Cancers Treated with Chemoradiotherapy

Purpose: A computer-assisted microvessel analysis system was developed to evaluate correlations between the architecture of biopsy specimen microvessels and the outcome for patients with esophageal cancer treated with chemoradiotherapy. Experimental Design: Biopsy specimens from 51 patients with esophageal cancer (T2-3, any N, M0) treated with chemoradiotherapy were immunostained with an anti-CD31 antibody and quantified using computerized image analysis. We evaluated the association of several microvessel factors with overall survival, including the ratio of total microvessel perimeter to total tumor area (TP/TA), the tumor hypoxic ratio, and the ratio of total microvessel number to total tumor area (TN/TA). Results from traditional manual microvessel density (MVD) hotspot count and computerized hotspot count were compared and the relation between hotspot MVD count and survival rate was evaluated. Results: The median follow-up time was 32 months. Both univariate and multivariate analyses revealed that computer-counted hotspot MVD and TN/TA and TP/TA ratios correlated significantly with the outcome of chemoradiotherapy. Kaplan-Meier survival curves showed that patients with high computer-counted hotspot MVDs and high TN/TA and TP/TA ratios had better overall survival rate than patients with low MVDs or ratios (P = 0.025, 0.008, and 0.031, respectively). Combining computer-counted MVD or TN/TA ratio with TP/TA ratio proved more predictive than any single factor. Two researcher-counted hotspot MVDs had no significant relation with outcome. Conclusion: Computer-assisted tumor microvessel analysis is a powerful tool in predicting the outcome for patients with esophageal cancer treated with chemoradiotherapy because intraobserver and interobserver variability is minimized.

[1]  Nils Lehmann,et al.  Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  K. Ang,et al.  Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: results of RTOG 9505. , 2005, International journal of radiation oncology, biology, physics.

[3]  M. Pompili,et al.  Prognostic factors for survival in patients with early-intermediate hepatocellular carcinoma undergoing non-surgical therapy: comparison of Okuda, CLIP, and BCLC staging systems in a single Italian centre , 2005, Gut.

[4]  Matthias Reimold,et al.  Prognostic impact of hypoxia imaging with 18F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. , 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  A. Harris,et al.  Hypoxia-Inducible Factor 1α Expression as an Intrinsic Marker of Hypoxia , 2004, Clinical Cancer Research.

[6]  Y. Rustum,et al.  Lack of Microvessels in Well-Differentiated Regions of Human Head and Neck Squamous Cell Carcinoma A253 Associated with Functional Magnetic Resonance Imaging Detectable Hypoxia, Limited Drug Delivery, and Resistance to Irinotecan Therapy , 2004, Clinical Cancer Research.

[7]  C. Mercke,et al.  Preradiotherapy Hemoglobin Level but not Microvessel Density Predicts Locoregional Control and Survival in Laryngeal Cancer Treated with Primary Radical Radiotherapy , 2004, Clinical Cancer Research.

[8]  H. Fujita.  Present status of esophageal cancer and its treatment in Japan. , 2004, Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia.

[9]  P. Berger,et al.  Christianity and Democracy: The Global Picture , 2004 .

[10]  A. Ochiai,et al.  Intratumor microvessel density in biopsy specimens predicts local response of hypopharyngeal cancer to radiotherapy. , 2003, Japanese journal of clinical oncology.

[11]  S. Groshen,et al.  Computerized Quantification of Tissue Vascularization Using High-resolution Slide Scanning of Whole Tumor Sections , 2003, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[12]  Johan Bussink,et al.  Pimonidazole binding and tumor vascularity predict for treatment outcome in head and neck cancer. , 2002, Cancer research.

[13]  R. Hetzer,et al.  Assessment of Survival in Patients With Primary Pulmonary Hypertension: Importance of Cardiopulmonary Exercise Testing , 2002, Circulation.

[14]  D. Girling.  Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial , 2002, The Lancet.

[15]  A. Harris,et al.  Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[16]  A. Ochiai,et al.  Image analysis of microvessel surface area predicts radiosensitivity in early-stage laryngeal carcinoma treated with radiotherapy. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  F. Bray,et al.  Cancer burden in the year 2000. The global picture. , 2001, European journal of cancer.

[18]  Y. Kitagawa,et al.  Improvement in the Results of Surgical Treatment of Advanced Squamous Esophageal Carcinoma During 15 Consecutive Years , 2000, Annals of surgery.

[19]  A. Ochiai,et al.  Potential role of microvessel density in predicting radiosensitivity of T1 and T2 stage laryngeal squamous cell carcinoma treated with radiotherapy. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[20]  G. Verlato,et al.  Induction Chemo-Radiotherapy for Squamous Cell Carcinoma of the Thoracic Esophagus: Long-Term Results of a Phase II Study , 1999, Annals of Surgical Oncology.

[21]  J. Cooper,et al.  Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. , 1999, JAMA.

[22]  J. Fraumeni,et al.  Changing patterns in the incidence of esophageal and gastric carcinoma in the United States , 1998, Cancer.

[23]  S. Roberts,et al.  High tumor angiogenesis is associated with poorer survival in carcinoma of the cervix treated with radiotherapy. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  D. Heresbach,et al.  Neoadjuvant chemotherapy and hyperfractionated radiotherapy with concurrent low-dose chemotherapy for squamous cell esophageal carcinoma. , 1998, International journal of radiation oncology, biology, physics.

[25]  C. Angeletti,et al.  Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study. , 1997, Journal of the National Cancer Institute.

[26]  A. Harris,et al.  Quantitation and prognostic value of breast cancer angiogenesis: Comparison of microvessel density, Chalkley count, and computer image analysis , 1995, The Journal of pathology.

[27]  J. Folkman,et al.  Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. , 1991, The New England journal of medicine.

[28]  M. Stelzner,et al.  Surgical therapy of oesophageal carcinoma , 1990, The British journal of surgery.

[29]  L. H. Gray,et al.  The Histological Structure of Some Human Lung Cancers and the Possible Implications for Radiotherapy , 1955, British Journal of Cancer.

[30]  A. Llombart‐Bosch,et al.  Angiogenesis in neuroblastoma: relationship to survival and other prognostic factors in a cohort of neuroblastoma patients. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  J. Laissue,et al.  Intratumoral microvessel density predicts local treatment failure of radically irradiated squamous cell cancer of the oropharynx. , 2000, International journal of radiation oncology, biology, physics.

[32]  W Vach,et al.  The prognostic value of angiogenesis by Chalkley counting in a confirmatory study design on 836 breast cancer patients. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[33]  Claudio Eccher,et al.  Microvessel density quantification in breast carcinomas. Assessment by light microscopy vs. a computer-aided image analysis system , 1995 .