Detection of p21WAF1/Cip1 in brain metastases.
Ruan S. Fuller G. Levin V. Bruner JM. Zhang W.
Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
The p21WAF1/Cip1 (p21) protein, a negative regulator of G1 checkpoint control, was overexpressed in the majority of human gliomas. To investigate whether p21 expression in brain metastases from various systemic origins is similar to that in gliomas and whether p21 expression is regulated differently in brain metastases and in corresponding primary tumors, we used immunohistochemical staining to examine the expression of p21 in paraffin-embedded sections prepared from primary colon and breast carcinomas and from metastatic brain tumors that originated from colon, breast, lung, and kidney cancers and from melanoma. Our results showed that 56% (28 of 50) of the brain metastases samples have more than 1% p21-positive staining cells compared with 87% of primary gliomas reported previously. Among the samples analyzed, p21 expression in brain metastases from breast carcinomas was much higher than in primary breast carcinomas. In contrast, p21 expression in brain metastases from colon carcinomas was less than primary colon carcinomas. The results from this pilot study suggest that p21 expression is regulated differently in metastatic and primary tumors.
Nervous system involvement by metastatic hepatocellular carcinoma.
Kim M. Na DL. Park SH. Jeon BS. Roh JK.
Department of Neurology, Seoul National University Hospital, Republic of Korea.
Nineteen patients with nervous system metastasis of hepatocellular carcinoma (HCC) were evaluated retrospectively. Nervous system metastasis was frequently initial presentation of HCC (seven out of 19 patients). Seven patients had metastases of the brain, of whom four had a stroke-like presentation. CT or MRI in these patients showed intracerebral hematomas in watershed areas. Enhancing lesion or edema adjacent to the hematoma helped differentiate these lesions from classical hypertensive hematomas. One patient with metastasis to the clivus presented with isolated six nerve palsy. The remaining 11 patients had spinal epidural metastases producing myelopathy in seven and radiculopathy in four. Radiation therapy failed to control the clinical course.
Stereotactic radiosurgery for brain metastases: comparison of lung carcinoma vs. non-lung tumors.
Williams J. Enger C. Wharam M. Tsai D. Brem H.
Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287-8811, USA.
In the medical literature, stereotactic radiosurgery (SRS) for brain metastases results in rates of local control of 65 to 85 %. To define patient selection criteria, we measured the survival in a population with a high proportion of non-small cell lung carcinoma (NCS lung) metastases that occurred soon after primary diagnosis. Between 9/89 and 10/93 30 adults (21 M, 9 F) had SRS for metastatic NSC lung carcinoma (14 patients) vs. non-lung carcinomas (16 patients having breast (3), renal (3), melanoma (3), GI (2, thyroid (1) or carcinoma of unknown origin (4)). The metastases were solitary for 22 patients and multiple for 8 patients. Average ages (y) (+/-SD) were 58.6+/-10.4 for NSC lung patients and 53.4+/-12.5 (p = 0.32) for non-lung patients. The average interval (months) from diagnosis of the primary to metastasis was 23.8+/-41.4 for all patients. This interval was shorter for NSC lung patients: 3.1+/-6.0 vs. 48.0+/-51.7 (p < 0.001) for non-lung patients. Twenty seven patients had conventional radiotherapy (XRT) before (24 patients) or after (3 patients) SRS. Doses (cGy) were 3303+/-841 for 13 NSC lung patients and 4256+/-992 for 14 non-lung patients (p = 0.034). The median time from primary diagnosis to SRS was shorter for the NSC lung patients (11 mo) compared to the non-lung patients (35 mo). SRS was given for recurrence of metastases after XRT for 11/14 NSC lung patients and 13/16 non-lung patients. The doses (cGy) of SRS were 1579+/-484 vs. 1682+/-476 (p=0.45) for the NSC lung and non-lung groups, respectively. After SRS a decrease in metastasis diameter was observed in 10 of 14 NSC lung patients vs. 12 of 16 non-lung patients (p=0.85 Chi-square). Twenty-seven of the 30 patients have died. For all patients, the median survival after diagnosis of the primary and after radiosurgery was 31.3 and 8.4 months, respectively. The median survival (95% CI) from primary diagnosis was 24.3 months (13.2-27.3) for NSC lung patients and 46.5 months (39.2-65.5) for non-lung patients (p=0.005 logrank test). The median survival (95% CI) after SRS was 7.9 months (3.0-14.3) for the NSC lung patients and 8.4 (2.9-11.9) months for the non-lung patients (p=0.98 logrank test). Within the two groups, no difference in survival was observed for patients who had SRS sooner (< 1 yr for NSC lung; < 3 yr for non-lung) after primary diagnosis: 9.3 vs. 6.5 mo for NSC lung (p=0.21) and 10.5 vs. 7.2 mo for non-lung (p=0.87). In this series, the shortened intervals from primary diagnosis to SRS for NSC lung metastases was associated with post-SRS survivorship that was equivalent to the more favorable non-lung group.