Unveiling the HER2-low phenomenon: exploring immunohistochemistry and gene expression to characterise HR-positive HER2-negative early breast cancer.

PURPOSE: HER2-low breast cancer (BC) is a novel entity with relevant therapeutic implications, especially in hormone receptor (HR) positive BC. This study examines whether HER2 mRNA through the 21-gene assay, Oncotype DX (ODX), can refine the diagnosis of HER2-low and HER2-zero, obtained by immunohistochemistry (IHC). METHODS: Between Jan 2021 and Jan 2023, 229 consecutive HR-positive HER2-negative early BC (T1-3 N0-1) have been characterised by IHC and ODX. HER2 status by IHC was either zero (IHC-0) or low (IHC-1 + and IHC-2 + /ISH-negative) while HER2-zero was further divided into HER2-null (IHC-0) and HER2-ultralow (IHC-1-10%). HER2 gene expression by ODX was negative if lower 10.7. RESULTS: The distribution of HER2 IHC was as follows: 53.3% HER2-0, 29.25% HER2-1 + , and 17.5% HER2-2 + . The clinicopathological characteristics were similar in the three groups, with higher PgR-negative rate in HER2-zero (13.9% vs 3% vs 5%). The distribution of RS was homogeneous in the three groups with the median HER2 gene expression of 9.20 [IQR: 8.70-9.60]. HER2 gene expression gradually increased as the IHC score, with substantial overlap. After adjusting for confounders, HER2-1 + and HER2 2 + had a significant positive correlation between HER2 gene expression and IHC [OR 1.42, 95% CI 1.21 to 1.68, p < 0.001; OR 1.96, 95% CI 1.61 to 2.37, p < 0.001] compared to the HER2-zero group. HER2 gene expression did not differ between HER2-null and HER2-ultralow subgroups. CONCLUSION: Due to the substantial overlap, the HER2 gene expression is unable to properly distinguish HER2-low and HER2-zero IHC whose accurate identification is critical in the context of HER2-negative BC.

Primary melanoma of the bladder: a case report and review of the literature.

OBJECTIVE: Primary bladder melanomas are rare and aggressive neoplasms. We herein described a new case and performed a review of the literature. PATIENTS AND METHODS: We present the case of a 81-year-old woman with a primary mucosal melanoma of the bladder after a history of acral melanoma (KRAS mutated) and lentigo maligna of the forehead. Using PubMed, we found that in literature 38 cases were described. RESULTS: In our patients, during a transurethral resection (TURBT), two bladder lesions were detected. The histologic exam revealed a malignant melanoma, Mib1/ki67: 10-12%, PDL1 <1%. No BRAF, NRAS or KRAS mutations were detected. She subsequently underwent a transurethral revision of the trigone and a partial cystectomy of the dome with bilateral pelvic lymph node dissection. Microscopical findings showed a residual 5 mm non-muscle-invasive melanoma of the bladder, with negativity of the surgical margins and of the 17 pelvic lymph nodes. No adjuvant treatment was proposed. To date the patient is disease-free. CONCLUSIONS: Primary bladder melanoma carries a poor prognosis and poses a therapeutic challenge to clinicians who manage patients with this rare condition. In our experience the multidisciplinary approach for the diagnosis and management of this rare cancer is mandatory.

Stroke care in the next decades: a projection derived from a community-based study in Umbria, Italy.

Recently published data show that stroke incidence is not longer declining, while case fatality rates has had a less pronounced fall in recent years than in the past. Projections of the increasing number of elderly people, combined with the greater risk of stroke in old age, suggest that in the forthcoming decades we will be faced with an increased request of health resources for patients with stroke. We have therefore used data from a community-based study on stroke incidence and outcome to project the number of first ever strokes, death from stroke and handicap from stroke in Italy, up to the year 2016. Results show that incidence will increase by 22.2%, and death at 6 months from first ever stroke by 29%. However, since patients already handicapped for other reasons are more likely to die from their stroke, the net number of newly handicapped persons will only increased by 5%. These results suggest that in the next decades the major increase in request of health care resources will result from the acute event and the immediate post-ictal phase, and not from the management of chronic handicap after a stroke.

Numerical analysis and DNA base compositions of some thermophilic Bacillus species.

Morphological, physiological, and biochemical characteristics and the DNA base compositions of 133 thermophilic Bacillus strains were determined. A total of 54 of these strains were received as identified species (mainly Bacillus stearothermophilus, Bacillus coagulans, Bacillus brevis, and Bacillus licheniformis) from international culture collections, and 79 newly isolated strains, which were isolated mainly from sugar diffusion juices of Italian plants, were also examined. Numerical taxonomy techniques (simple matching coefficient and unweight pair grouping using the mathematical average) and DNA G + C values showed that the strains aggregated into nine clusters. Both B. licheniformis and B. brevis were well separated from the other organisms. B. stearothermophilus and B. coagulans were confirmed as separate clusters and exhibited greater heterogeneity than previously shown. The B. stearothermophilus strains clustered into four groups, three of which have been recognized previously by other authors; the members of the fourth group had distinctive characteristics, including considerable biochemical inertness, an inability to grow at temperatures greater than 60 degrees C, and a high G + C content. Within the B. coagulans cluster the strains with characteristics very similar to those of the new species Bacillus smithii clustered together. However, the remaining strains were still clearly separated into two groups; one of these groups was considered B. coagulans sensu stricto, and the other was distinguished by morphological and biochemical criteria, such as spores which do not swell the sporangia, utilization of citrate, a higher proteolytic activity, and acidification of some carbohydrates. Our results were confirmed by comparing them with distinctive characteristics of recently described thermophilic Bacillus species.

Parallelism in the mortality clustering of the most frequent cancer sites in Italy and in the Marche region.

Clusters of selected cancer sites mortality, regarding Italy and the Marche region, were compared. Very similar associations were found both in males and in females, in particular between the alcohol-tobacco-related sites. Many clusters agree with the international literature, while others could constitute a starting point for formulating new hypotheses.

Gastric and lung cancer mortality in the Marche region of Italy, 1980-1983.

This paper describes patterns in gastric and lung cancer mortality in the Marche region of Italy and in its 24 Local Health Districts (LHD) over the period 1980-83. Mortality data were obtained from the magnetic tapes provided by the National Institute of Statistics. Linear regressions were tested with the aim to relate the AADRs with the proportion of the agricultural workers in the 1951, 1961 and 1971 census years. The results obtained show that, in the whole Marche region, mortality from lung cancer is first in male cancer mortality. However within the Region itself many LHDs had different patterns. Among the LHDs, gastric cancer rates were the highest in some northern mountain zones, and lung cancer rates in some central coastal zones. Statistical analyses emphasize the inverse relationship between the male 0-64 AADRs relative to gastric cancer and those of lung cancer in the 24 LHDs. Among these, the male gastric cancer 0-64 AADRs are significantly and directly related to the proportion of farm workers in 1971, and the female ones to the proportion of farm workers in all the three periods, which in turn are always inversely related to the 0-64 AADRs male lung cancer. The differences between the observed and expected death frequencies in the several LHDs stress the results obtained in the present study, which generally agree with those obtained in other studies regarding the same and neighbouring areas and with those reported by the international literature.

[Descriptive epidemiology of malignant tumors of the colon and rectum]. / Epidemiologia descrittiva dei tumori maligni del colon e del retto.

This paper examines patterns and trends of colon and rectal cancer in different countries and in Italy. Incidence and mortality rates of colorectal cancer vary widely in the world. High rates are characteristic of highly developed countries in North America, northern and western Europe. The lowest rates are found in Asia, Africa and most Latin American countries. The most recent incidence rates for colon cancer from cancer registries around the world published in "Cancer Incidence in Five Continents, 1982" range from 0.6 cases per 100,000 in Dakar, Senegal to 32.3 in Connecticut, USA for males and from 0.7, always in Dakar, to 27.4 among the Japanese population of Bay Area, USA. The Italian cancer registry for Varese, shows a rate of 19.9 for males and 16.9 for females. The incidence rates for cancer of the rectum range from 1.5 per 100,000 in Dakar to 22.6 in the North West Territory and Yukon, Canada. For females the highest rates, 13.9, are in Israel (born in Europe or America) and the lowest always in Dakar, 1.0. The Varese rates are 15.7 and 9.1 for males and females respectively. Regression analysis shows that between incidence rates of colon and rectal cancer, divided by sex, there is a strict correlation. The sex ratios for colon and rectal cancer differ, rectal cancer being distinctly more common among males in most countries, whereas colon cancer affecting both sexes at rather similar rates. Results confirm that there is a higher frequency, for colon cancer in particular, in urban areas than in rural areas. Differences due to race, on the contrary, have found no confirmation. The international incidence trends over the period 1960-1980 show a general increase for colon cancer in both sexes. In Asia the most evident increase have been in Singapore and Miyagi. In Europe, Slovenia (Yugoslavia) and Norway present 40-50% increases. Similar tendencies have been observed for rectal cancer trends. Values more than increase 100%, for both sexes, have been found in Hawaii and Singapore. In Europe, Norway and Slovenia always present the highest increases. Marked geographic variations occur even as regards colon and rectal mortality in the different countries. The highest values for colon cancer have been found in Luxemburg (18.4) for males, and in New Zealand (13.3) for females and the lowest in Honduras for both sexes (0.1 and 0.0 respectively). In Italy the values are 8.0 for males and 6.0 for females.(ABSTRACT TRUNCATED AT 400 WORDS)

Tobacco smoking, coffee, cocoa and tea consumption in relation to mortality from urinary bladder cancer in Italy.

This paper examines changes in mortality from urinary bladder cancer in Italy during the years 1950-81 in relation to changes in smoking habits and in coffee, cocoa and tea consumption. The authors found that, in both sexes and for all ages, mortality has been increasing throughout this period, although the rates and relative increase have consistently been much lower and more gradual for women than for men. From the analysis of age-cohort-period variation it seems that bladder cancer mortality can also be influenced by changes in smoking habit patterns and by variation in the quality of diagnoses. The increase in death risk for both sexes in Italy up to cohorts born around 1905-10 can be related to occupational exposures and to high-tar-content tobacco smoking, whereas the tendency for mortality rates to stabilize and decline in cohorts born after 1910 were influenced by changes from high-tar-content and no-filter cigarettes to low-tar-content and filter cigarettes and by prevention measures taken in at-risk working environments. The consumption of coffee, cocoa and tea does not seem to be related to the increase in bladder cancer risk in Italy.

Characterization of some Clostridium species by gas-liquid chromatography using numerical analysis.

We studied 42 strains of Clostridia belonging to 20 different species. All the strains were examined for morphological characters, biochemical reactions, and analyzed by means of gas-liquid chromatography (GLC) to determine metabolic patterns of short chain fatty acids and alcohols. To increase the number of criteria for the differentiation, specimens were grown on Peptone Yeast Extract medium (PY) with the addition of 13 different carbohydrates. The strains were compared using numerical taxonomic techniques based upon 20 unit qualitative and 224 quantitative characters. Data were examined using the simple matching coefficient (SSM) for qualitative characters, and degree of overlap between superimposed trace (So) for qualitative characters, and clustering was achieved using the unweighted pair group method with arithmetic averages (UPGMA) technique. DNA base composition was also determined. Numerical analysis showed remarkable difference between phenograms derived from SSM and So coefficients. The phenogram (SSM) is formed by 11 clusters and eight of these include strains from only one species. Only three clusters contained strains from different species. The cluster variability range of G + C base composition was never higher than 4 mol% except for one cluster where it reached 7 mol% G + C. In the phenogram (So) instead, there are 8 clusters and in only one case are strains from one species aggregated. In the remaining 7 clusters strains belonging to two or more species aggregated. The range values of base composition are over 4 mol% in three of the eight clusters.

Esophageal cancer mortality: relationship with alcohol intake and cigarette smoking in Italy.

This paper examines changes with time in age-adjusted mortality from esophageal cancer for the years 1950-1981, in relation to changes in smoking habits and alcohol consumption. In both sexes the age-adjusted death rates have shown no marked time variation. Instead in the same period there have been marked temporal variations in consumption of alcohol and tobacco which are considered risk factors associated with esophageal cancer. The male cohort variation seems to indicate some fluctuations in mortality before 1921 and a progressive increase after this year. In females the death rates are very low and the cohort variation is practically constant. The progressive increase of cohort variation in esophageal cancer mortality for men born after 1921 coincides with a progressive increase in hard alcohol consumption. In the same period there has also been a progressive increase in tobacco consumption but this begun at the turn of this century.

Mortality from prostate cancer in Italy: 1950-1979. Cross-sectional rates and cohort analysis.

This paper studies prostate cancer mortality in Italy from 1950-1979 to evaluate its importance in relation to total cancers, examine the time trend for forecasting future mortality trends, and makes an attempt to interpretate mortality by analyzing demographic and risk factors. In the Authors' opinion findings from cross-sectional rates, cohort analysis and Devesa-Schneiderman method, indicate that in Italy even if the age-adjusted mortality rate has nearly doubled over the period, as in many other countries, mortality can be expected to remain constant or decrease in the future, since the data to hand show a decreasing trend in some age cohorts.

[Characterization of species of the genus Clostridium by gas chromatographic analysis of the fatty acids produced during metabolism]. / Caratterizzazione di specie del genere Clostridium mediante analisi gas-cromatografica degli acidi grassi prodotti dal metabolismo.

Volatile and non volatile fatty acids deriving from the bacterial metabolism of different sugars were determined by gas-chromatography to better characterize Clostridium tertium and Clostridium ramosum. The data obtained were also used for numerical taxonomic analysis and dendrograms were elaborated to study the taxonomic relationships between the two species.

[Isoproterenol in the emergency treatment of cardiac stimulus conduction]. / L'isoproterenolo nel trattamento di emergenza delle turbe della conduzione dello stimolo cardiaco

Continuous infusion with isoproterenol (mean dose 2 mug/min) was carried out for periods of a few hours to a few days in 22 patients recurrent Adams-Stokes syncope. In all cases, an improvement leading to or in the direction of physiological cardio-circulatory conditions was noted. Undesired side-effects foreseeable as the result of beta-adrenergic stimulation were not observed. Isoproterenol is more active than metaproterenol and is to be preferred on this account. It is indicated in Adams-Stokes crises due to conduction disturbances when pacemakers cannot or should not be fitted, or as a prelude to their application.