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January 2002

Immunohistochemistry as a predictor of long-term survival in PMM
Pleural malignant mesothelioma is a rare and usually rapidly fatal tumor. The median survival is four to 12 months, but a small subset of patients experience considerably longer survival. The authors of this study evaluated the utility of the cell cycle-related proteins p27kip1 and MIB-1 as prognostic indicators in PMM. Staining results from 27 patients who survived longer than 24 months were compared with those from 36 patients who survived less than 24 months. The expression of p27kip1 was significantly higher in the long-term survivors than the short-term group (81.41 versus 31.94 percent; P<0.0001). This antigen was more commonly expressed in epithelioid than biphasic tumors. Conversely, MIB-1 immunoreactivity was significantly greater in short-term than long-term survivors (43.53 versus 14.11 percent; P<0.0001) and was more commonly associated with the biphasic phenotype. A combination of these two antigens identified long- and short-term survivors with a 100 percent sensitivity and specificity. Approximately 50 percent of short-term survivors died in less than 10 months while long-term survivors did not reach 50 percent mortality until 40 months. The authors concluded that p27kip1 and MIB-1 provide important prognostic information about PMM.

Bongiovanni M, Cassoni P, De Giuli P, et al. p27kip1 immunoreactivity correlates with long-term survival in pleural malignant mesothelioma. Cancer. 2001;92:1245-1250.

Reprints: Dr. Gianni Bussolati, Dept. of Oncology, University of Turin, Via Santena 7, 1-10126 Torino, Italy; bussolati@monlinette.unito.it

Role of histologic grade in managing cancers of the head and neck
The authors evaluated the role of histologic grade (World Health Organization criteria) as an independent predictor of distant metastases for carcinomas of the head and neck. They studied 1,266 consecutive patients treated with definitive or postoperative radiotherapy between 1989 and 1997. All patients received at least 50 Gy, and all stages and subsites of head and neck cancers were included. The authors found a strong correlation between grade and N stage (P<.000001). The metastases-free survival was 98 percent, 90 percent, and 72 percent for grades one, two, and three, respectively (P<.000001). For stage N0 patients, metastases-free survival was greater than 90 percent, regardless of grade. For N1 patients, it was greater than 90 percent for grades one and two tumors but dropped to 75 percent for grade three tumors (P=.001). For patients with N2 and N3 disease, metastases-free survival was 91 percent, 79 percent, and 59 percent for grades one, two, and three, respectively (P=.008). Similar findings were noted when only neck control was analyzed. The authors concluded that patients with grades one and two tumors are at low risk for distant metastases, except for those within N3 disease. Patients with grade two and N3 disease and those with grade three disease with any lymph node metastases have a high rate of distant metastases and should be considered for systemic treatment.

Fortin A, Couture C, Doucet R, et al. Does histologic grade have a role in the management of head and neck cancers? J Clin Oncol. 2001;19:4107-4116.

Reprints: Dr. André Fortin, Dept. of Radiation-Oncology de l’université Laval, L’Hôtel-Dieu de Québec, 11 Cte du Palais, Québec, Canada GIR 2J6; afortin@videotron.ca

Arrhythmogenic right ventricular cardiomyopathy
The authors of an Italian study subclassified the patterns of fatty infiltration observed in 27 patients (12 autopsies, 15 heart transplants) with arrhythmogenic right ventricular cardiomyopathy who were seen at two referral university hospitals. They divided the patients into two groups: infiltrative with a lace-like pattern of transmural fatty infiltration and strands of normal residual cardiomyocytes (n=11), and cardiomyopathic with massive replacement by fibro-fatty tissue and cardiomyopathic changes such as hypertrophy and myofibril loss of residual cardiomyocytes (n=16). Hearts from the infiltrative group primarily were obtained at autopsy from patients who died suddenly. In this group, fatty substitution was limited almost exclusively to the right ventricle, and mitral valve dysplasia was often present. Hearts from the cardiomyopathic group were primarily from heart transplant patients with congestive heart failure. Fibro-fatty replacement was more extensive because it was usually biventricular. Despite these differences in clinical outcome and morphologic features, the patients in the two groups were similar with regard to age, sex distribution, occurrence of life-threatening ventricular arrhythmias, and prevalence of family history of sudden death, arrhythmias, and cardiomyopathy. The authors claim that the infiltrative and cardiomyopathic patterns present different clinical and pathological subsets of arrhythmogenic right ventricular cardiomyopathy. They say that differentiating between the two patterns on endomyocardial biopsy is feasible and could provide important prognostic information.

D’Amati G, Leone O, Di Gioia C, et al. Arrhythmogenic right ventricular cardiomyopathy: clinicopathologic correlation based on a revised definition of pathologic patterns. Hum Pathol. 2001;32:1078-1086.

Reprints: Dr. Pietro Gallo, Dipartimento di Medicina Sperimental e Patologia, Sezione di Anatomia Pathologica, Policlinico Umberto I, Viale Reginal Elena 324, 00161 Roma, Italy

An immunohistochemical marker of prostate carcinoma
The authors described a molecular marker of prostate carcinoma, P504S, that appears to be highly sensitive and specific and may be useful in diagnostically difficult cases. Cases of prostate carcinoma (n=137) and benign prostatic tissue (n=70) were studied in paraffin for expression of P504S using a monoclonal antibody. All cases of prostate carcinoma reacted strongly. In 92 percent of the cases, more than 75 percent of glands/cells were strongly positive (continuous and dark cytoplasmic or apical granular pattern), irrespective of Gleason score. In two percent of cases, however, less than five percent of glands/cells reacted strongly. In contrast, benign prostate tissue was negative for this marker in 88 percent of cases. In 12 percent, weak staining (single cells or groups of epithelial cells with a discontinuous and weakly granular pattern) was noted. The staining pattern was useful in identifying small foci of tumor (<1 mm) in needle biopsy specimens, as well as residual minimal carcinoma following radiation therapy. Immunocytochemical staining for P504S may be a useful adjunct in identifying prostate carcinoma in routine clinical practice.

Jiang Z, Woda BA, Rock KL, et al. P504S. A new molecular marker for the detection of prostate carcinoma. Am J Surg Pathol. 2001;25:1397-1404.

Reprints: Dr. Zhong Jiang, Dept. of Pathology, University of Massachusetts Medical School, 55 Lake Ave., Worcester, MA 01655; jiangz@ummhc.org

Classifying pN0 and pNX
A one-page communication published in Cancer clarifies the position of the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) regarding pN0. Although the 1997 TNM classification of the AJCC and the UICC includes statements such as, "Histologic examination of a regional lymphadenectomy specimen will ordinarily include 12 (for colorectal carcinoma) or more lymph nodes," one should be aware that these are guidelines, not requirements. According to the TNM supplement of 1993, lymphadenectomy specimens containing a less than recommended number of nodes are classified as pN0 rather than pNX.

Sobin LH, Greene FL. TNM classification: clarification of number of regional lymph nodes for pN0. Cancer. 2001;92:452

Reprints: Dr. Leslie H. Sobin, GI Pathology, Armed Forces Institute of Pathology, 14th St. and Alaska Ave., Washington, DC 20306; sobin@afip.osd.miln