Massimo Scheibel

Breast cancer in young women: clinicopathological features and biological specificity

Literature data suggest that breast cancers occurring in young patients may be different from those arising in older women. In this study the clinicopathologic characteristics of 50 patients under 40 years of age were compared with those of patients aged over 60. Patients under 40 years old more frequently had a family history of breast cancer than did older patients (24% vs 17%) and had more often used oral contraceptives (29% vs 13%); on average they had experienced menarche 1 year earlier. For early onset breast carcinomas there was a higher frequency of grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs 58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2 overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate that breast cancers arising in young women have a significantly different biopathological profile from those in older patients, with a predominance of unfavourable prognostic parameters.

Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based chemotherapy in advanced non-small cell lung cancer.

PURPOSE Tumors with p53 overexpression have been associated with enhanced resistance to cisplatin-based chemotherapy in a few and small studies involving non-small cell lung cancer. The relationships and interactions between p53, Rb and bcl-2 immunostaining, clinical parameters and response to cisplatin-based chemotherapy were evaluated in the present study. EXPERIMENTAL DESIGN Histological specimens obtained by bronchial or fine-needle biopsy from patients who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated by immunostaining. RESULTS There were 102 patients, 88 men. Median age was 63 years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%) had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group with p53 positive immunostaining was 26% versus 57% of the p53 negative group (P=0.004). In multivariate analyses p53 positive immunostaining was identified as an independent predictive factor for resistance to cisplatin-based chemotherapy (P=0.006). CONCLUSIONS Our study confirmed an association of p53 immunostaining and response rate of patients treated with cisplatin-based chemotherapy.

Primary Cutaneous Leiomyosarcoma: A Clinicopathological and Immunohistochemical Study of 7 Cases:

Primary cutaneous leiomyosarcomas are rare tumors, few series being reported in the current literature. A retrospective study of 7 cases was undertaken to understand the clinicopathological characteristics of these neoplasms and some of their molecular mutations. Histologically, a well-differentiated proliferation of cells of smooth muscle derivation was evident in all cases. The number of mitoses was considered the most important criterion of malignancy (more than 2 for 10 HPF). Smooth muscle actin, desmin, and vimentin were positive in all cases. Immunohistochemical analysis also revealed a positivity for p53 in 3 cases and no reaction for retinoblastoma protein. Research for Epstein-Barr virus was negative in all cases. Three patients developed local recurrences owing to incomplete surgical excision. Recurrent tumors were more atypical and located deeper. No distant metastases were observed. Our results emphasize that cutaneous leiomyosarcomas have an indolent biological course if treated by surgical excision with wide margins. Molecular abnormalities involving tumor suppressor genes are probably involved.

Metachronous malignancies in men with previous prostate cancer in Umbria, Italy, 1994-2003

Data about second primary tumors after prostate carcinoma are controversial. Some authors emphasize an increased incidence of some cancer sites, others an overall diminution. With the aim to provide further information to define the issue, we have analyzed the frequency of second metachronous primary malignancies in patients with diagnosed prostate cancer in the Umbria region of Italy. A total of 410 metachronous cancers among 4528 prostate cancer patients were abstracted from incident cases of the RTUP, over the period 1994–2003. This cohort was compared with all cases (except prostate cancers) recorded in the RTUP archive. The expected number of cases was obtained from indirect standardization with regional incidence rates of several sites. The significance of the observed/expected ratios and the corresponding 95% confidence intervals were based on the Poisson distribution. A significant standardized incidence ratio was found for all sites but prostate, with 410/351 observed/expected cases. The significance disappears considering all sites except prostate and skin non-melanomas. Among several sites, significant standardized incidence ratios were found for skin non-melanomas, for bladder, for rectum, but not for colon cancers. Kidney, ureter and urethra showed a nonsignificant standardized incidence ratio. Nasopharynx showed a significant standardized incidence ratio, but the result was based on a very small number of cases. In our data, the increase in urinary bladder and rectal cancers, after prostate cancer diagnosis, seems to be real: it is plausible that the number of second cancers may be due to increased urologist surveillance, which, in our Region, does not seem to be reduced in elderly men.

INCIDENCE OF MULTIPLE PRIMARY BLADDER AND PROSTATE CANCER IN A CENTRAL REGION OF ITALY. UMBRIA, 1994-2004

The aim of this study was to determine the incidence of multiple bladder-prostate cancers in the population of the Italian region of Umbria and to clarify some diagnostic aspects. Prostate and bladder cancer incidence data in Umbria were obtained from cancer registry records. In the period from 1994 to 2004, 3,470 new patients with bladder cancer and 5,430 new patients with prostate cancer were registered. Among these patients there were 238 who presented multiple bladder and prostate cancers. Synchronous cancers were detected in 74 of these patients. Fifty-four of them had simultaneous tumors (diagnosed during the same hospitalization), while in 16 patients bladder cancer was detected earlier than prostate cancer and in 4 patients the opposite occurred. This study confirmed an increase in prostate cancer diagnoses in patients with bladder cancer. The increase was mainly accounted for by the detection of prostate cancers during cystectomies performed for bladder carcinoma.

Urban-rural differences in male cancer incidence and mortality in the Umbria region of Italy

Background: The aim of this study is to verify the existence of different rates of cancer incidence and mortality in males in the urban and rural populations of Umbria and to formulate hypotheses as to why this occurs. Methods: Directly age-adjusted incidence rates (AAIR) and age-adjusted death rates (AADR) were calculated for 1998-2002 and the expected number of rural cases (standardized incidence ratios-SIRs and standardized mortality ratios-SMRs) was determined by indirect standardization using urban incidence and mortality. Results: Urban zones have higher AAIR’s for the most common cancer sites. Significantly lower SIRs, in rural areas, were shown for skin melanoma, prostate and bladder cancers and a significantly lower SIR was also determined for the combination of all cancer sites. Lower AADRs in rural areas were demonstrated for the most common cancer sites and significant low SMRs were shown for lung cancer and skin melanoma. Prostate cancer incidence is significantly higher in urban areas whereas the mortality rate is slightly higher in rural municipalities probably due to the effects of the opportunistic screening widely available in Umbria, particularly in zones near diagnostic services. A very similar pattern was found for urinary bladder cancer; this could be related to the association between prostate and bladder cancer sites. Both incidence and mortality from melanoma are significantly lower in rural areas, this may be due to the difficulty in accessing diagnostic services or/and to different occupational exposure patterns. Conclusion: It would appear in Umbria that differences in health services utilization continue to exist. In particular, our results are compatible with a lower diffusion of preventive activities for prostate cancer and skin melanoma in rural areas.

EPIDEMIOLOGY OF COLORECTAL CANCER IN THE UMBRIA REGION OF ITALY: PRESCREENING PERIOD

Aims and background The epidemiology of colorectal cancer in Umbria, Italy, was evaluated, and data were analyzed in the pre-screening period to better understand the etiology of the disease and to develop screening strategies. Materials and methods Incident data were collected by the Umbrian Population Cancer Registry and mortality data by the Nominative Regional Mortality Registry from 1994 to 2002. The survival rates relative to Italian cancer registries were derived from the Italian Associations of Cancer Registries publications. Time trends were analyzed by joinpoint regression. The follow-up for survival rates referred to December 31, 2005. Results The trend of colorectal cancer age-adjusted incidence showed a slight, constant, but non significant increase over time. The mortality trend showed a slight, constant, but non-significant decrease. Age at diagnosis remained constant in males, whereas in females it showed a significant increase of about 1.5 years. In the last period, all incidence rates increased with age, but in males they presented a rapid increase in the 55-74 age group, levelled and declined up to 84 and after again reached, which could be a consequence of opportunistic screening practice, probably undergone by males. Mortality in both sexes increased with age, whereas survival rates fell. Comparison of survival rates in some Italian cancer registries showed that the Umbria region, in the 1994-1996 period, was the zone with the highest relative survival; in the 1996-1999 period, the rate stopped, differently from other Italian zones. In the last period, the highest survival rates were recorded by registries covering zones with active screening programs. Conclusions The present reduction of mortality in Umbria, as in other Italian areas, is dependent on the natural behavior of the disease, which is linked to a birth cohort-related effect of stabilization and decrease in exposure to risk factors.