Tumor oxygenation correlates with molecular growth determinants in breast cancer.
Hypoxic tumor cells may represent a fraction of cells that are not susceptible to radiation or chemotherapy. Intratumoral oxygen partial pressure (pO2) is the result of oxygen delivery and consumption. Cell proliferation is one factor to effect oxygen consumption and we therefore studied the correlation between tumor pO2 and histological parameters.


METHODS
In 36 women and one man (age range 29-80 years) with suspected breast cancer. Before tumor resection, intralesional pO2 was determined with a polarographic needle electrode. Under ultrasound control, 200 tumor measurements were obtained; Hb levels, Hk, arterial blood gas parameters, and tissue temperature were determined. The median of pO2 values and the percentage of hypoxic areas (pO2 < 10 mmHg) were calculated and correlated with the histological type, grading, ER, PR, and the expression of Ki-67, p53, EGFR, pS2, and c-erb-B2.


RESULTS
The overall median pO2 was 44 mmHg, and 1024 measurements (13.8%) represented hypoxic areas. Ductal and lobular invasive cancers showed median pO2 of 41 mmHg. The mean pO2 of G1 tumors was 59 mmHg and the hypoxic fraction 8%, in contrast to G2 tumors with 43 mmHg and 17%, and G3 tumors with 36 mmHg and 20.4% (p < 0.01). We observed a correlation with tumor size and an increased rate of hypoxic areas in T3-4 lesions (p < 0.02). Also tumors with negative nodes or positive ER had significantly higher pO2 values, as did tumors with an overexpression of c-erb-B2, p53, and cathepsin D.


CONCLUSIONS
Oxygenation of human breast cancers can safely be measured in patients prior to surgical therapy. pO2 values correlate both with prognostic markers examined histologically and with molecular growth factors. As the efficacy of preoperative or adjuvant treatment in individuals may depend on oxygen partial pressure, efforts to manipulate tumor pO2 for therapeutic purpose could be promising.
Hohenberger
P
P
Division of Surgery and Surgical Oncology, Robert-Rössle Hospital and Tumor Institute, Humboldt University, Berlin, Germany. hohenberger@rkk.berlin.de
Felgner
C
C
Haensch
W
W
Schlag
P M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D002402:Cathepsin D / Q000378:metabolism; D002455:Cell Division; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000032:analysis; D010101:Oxygen Consumption; D010313:Partial Pressure; D011960:Receptors, Estrogen / Q000378:metabolism; D016217:Ultrasonography, Mammary
D011960:Receptors, Estrogen; D002402:Cathepsin D; D010100:Oxygen