Divergence of annual and perennial species in the Brassicaceae and the contribution of cis-acting variation at FLC orthologues.

Variation in life history contributes to reproductive success in different environments. Divergence of annual and perennial angiosperm species is an extreme example that has occurred frequently. Perennials survive for several years and restrict the duration of reproduction by cycling between vegetative growth and flowering, whereas annuals live for 1 year and flower once. We used the tribe Arabideae (Brassicaceae) to study the divergence of seasonal flowering behaviour among annual and perennial species. In perennial Brassicaceae, orthologues of FLOWERING LOCUS C (FLC), a floral inhibitor in Arabidopsis thaliana, are repressed by winter cold and reactivated in spring conferring seasonal flowering patterns, whereas in annuals, they are stably repressed by cold. We isolated FLC orthologues from three annual and two perennial Arabis species and found that the duplicated structure of the A. alpina locus is not required for perenniality. The expression patterns of the genes differed between annuals and perennials, as observed among Arabidopsis species, suggesting a broad relevance of these patterns within the Brassicaceae. Also analysis of plants derived from an interspecies cross of A. alpina and annual A. montbretiana demonstrated that cis-regulatory changes in FLC orthologues contribute to their different transcriptional patterns. Sequence comparisons of FLC orthologues from annuals and perennials in the tribes Arabideae and Camelineae identified two regulatory regions in the first intron whose sequence variation correlates with divergence of the annual and perennial expression patterns. Thus, we propose that related cis-acting changes in FLC orthologues occur independently in different tribes of the Brassicaceae during life history evolution.

Relationships between age, mammographic features and pathological tumour characteristics in non-palpable breast cancer.

Non-palpable breast cancers are often in situ or smaller and have less nodal and distant metastases than palpable lesions. They represent a heterogeneous group of tumours, which may have different prognostic behaviour. We analysed a retrospective series of 982 non-palpable breast cancers assessed histologically at the National Cancer Institute of Milan from 1985 to 1995, following pre-operative mammography-guided localization. The association between mammographic data (parenchymal pattern and findings), patient age and tumour histology was investigated by review of clinical records and statistical modelling. We also investigated the association between the presence or absence of microcalcification as a mammographic finding and pathological tumour characteristics (tumour size, axillary nodes status and grading) or receptor status for oestrogen (ER) and progesterone (PgR). In situ disease or invasive tumour with an intraductal component, whether extensive or not, were commoner in young women and mammography more frequently showed a dense parenchymal pattern and microcalcifications in these cases. In older women (55 years or more), a fatty breast pattern, nodular opacities with or without microcalcifications, and invasive tumours of the ductal, lobular, mixed or other types were closely related. When the relationships between mammographic findings, pathological tumour characteristics and receptor status were investigated for invasive cancers, there was an association between the presence of microcalcifications and less favourable tumour characteristics.

BMRI in early detection of breast cancer in patients with increased genetic risk: our preliminary results.

Because of the higher risk of developing breast cancer and the early onset of the disease in women proved or suspected to be carriers of a breast cancer susceptibility gene, a dedicated screening should be offered as a less invasive approach with respect to the otherwise suggested prophylactic mastectomy. This should be optimized in order to overcome the limitations of conventional breast imaging with the application of new technologies such as Breast Magnetic Resonance Imaging (BMRI). A diagnostic protocol for routine control in patients with high risk for developing breast cancer has been prepared. Within a 7 months period, 23 patients suspected or proved to carry a breast cancer susceptibility gene underwent BMRI. Four breast cancers were identified with BMRI. In these cases mammography was negative because of the density of the parenchyma or for its fibroglandular pattern. US was negative in two cases, not specific for malignancy in one case and considered as only possibly malignant but with biopsy recommendation on the basis of MR findings in the last one. Clinic analysis was positive for mass in two cases. The accuracy of BMRI is known to be higher than that of conventional imaging in the study of breast parenchyma. High spatial resolution and no breast density influence can give more detailed information about smaller lesions and the right extent of the disease.

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Hysterosalpingography in the sequels of conisation of the uterine cervix.

A hysterosalpingographic survey was made of 65 women of reproductive age who had undergone conisation of the uterine cervix for carcinoma in situ or severe dysplasia at least one year before. None of the patients investigated radiologically had undergone uterine surgery before conisation. In a high percentage of cases morphological changes of the cervical canal and, less frequently, the isthmus were found. Most of the changes are attributable to scar retraction, and the hysterosalpingographic findings did not differ appreciably from those following other types of gynecological surgery, namely, segmental or total stenosis and ectasia of the cervical canal and isthmus. A control series of patients with preoperative and postoperative hysterosalpingograms is now under consideration to confirm the radiological findings and to correlate them with clinical data.

Nipple discharge as a sign of preneoplastic lesions and occult carcinoma of the breast: clinical and galactographic study in 103 consecutive patients.

A clinical and galactographic investigation was carried out on 103 patients with hematic, serous-hematic, and serous nipple discharge. The age of the patients ranged from 18 to 72 years. A single papilloma was found in 20 cases, diffuse papillomatosis in 2 cases, atypical ductal hyperplasia in 8 cases, and ductal carcinoma in 4 cases (3 of these were infiltrating and 1 was noninfiltrating associated with a diffuse papillomatosis). Mammography gave no indications of carcinoma in any of the 4 cases. In the remaining 49 patients, pictures of ductal hyperplasia, periductal mastitis or sclerosis, sclerosing adenosis, or ductal ectasia were observed. The various types of lesions were often associated. Lacunae, stenosis, or occlusion of the ducts, evidenced by galactography, correlated well with the histologic findings of proliferative lesions of the ductal epithelium. Nevertheless, in practice, it should be the type of discharge that indicates surgery rather than galactographic or cytologic data, which appeared to have little diagnostic value. The frequency with which preneoplastic (or limit) lesions, and also nonsuspect carcinomas were found in patients with a significant nipple discharge confirm the importance of this symptom for a secondary prevention of early diagnosis of mammary neoplastic lesions originating from galactophorous ducts. Finally, complete resection of the galactophorous ducts must be considered as the best treatment in all patients with a suspicious nipple discharge that requires surgery.

[Teleradiography and tomography in the search for pulmonary metastases in 132 cases of soft tissue and bone neoplasms]. / Teleradiografia e tomografia nella ricerca delle metastasi polmonari in 132 casi di neoplasie delle parti molli e delle ossa.

In recent years whole lung tomography (WLT) has been considered mandatory in the staging of some neoplastic diseases, particularly of soft tissues and bone tumors. Since WLT is an exacting roentgen examination, its usefulness was evaluated by analysing 132 consecutive patients submitted to orthogonal chest roentgenograms and WLT, from January 1979 to October 1981 at the National Cancer Institute of Milan. A comparison between WLT and traditional chest X-ray examination was performed in order to evaluate how much tomography is significantly useful in improving diagnosis of lung metastases. From this analysis, the authors conclude that WLT is generally unnecessary when chest roentgenograms are negative, whereas it is useful when single or multiple lung metastases are already evident by traditional X-ray examination. In these cases WLT allows a more accurate identification of the metastases from the point of view of their number and site, which is important not only for the treatment choice but also for the check of its effectiveness.

Lobular breast cancer: how useful is breast magnetic resonance imaging?

RATIONALE AND OBJECTIVES: To review magnetic resonance imaging (MRI) findings in lobular breast carcinoma, the in situ or infiltrating subtype, with special attention to the dynamic curves with the aim to evaluate possible differences with ductal carcinoma. METHODS: In 2 years, 27 patients with lobular and one with tubular carcinoma underwent MRI at the Istituto Nazionale Tumori of Milan. RESULTS: All lobular carcinomas demonstrated early or late enhancement (100% sensitivity), without significant differences in morphology compared with ductal carcinoma, but frequently with a different shape of the dynamic curves. CONCLUSIONS: Due to its infiltrative growth associated to only limited connective tissue reaction, lobular carcinoma often encounters difficulties in mammographic diagnosis. In contrast, MRI can be very helpful in evaluating the true extension of the disease, especially when breast conservation is considered. Due to a more consistent fibrotic stroma, these lesions sometimes show a delayed enhancement, which suggests that more than one set of subtracted images should be evaluated during MRI analysis.

[Role of thermography in the diagnosis of breast neoplasms]. / Il ruolo della termografia nella diagnosi delle neoplasie mammarie.

319 cases of breast pathology of doubtful clinical diagnosis were studied by means of thermography and mammography, with histological verification: 214 proved to be malignant tumours and 105 benign. The role of thermography is discussed on the basis of these results; it would appear to be restricted to diagnostic aid status associated with other procedures, particularly clinical examination and mammography.

[Comedocarcinoma of the breast: mammographic and thermographic evaluation of 52 cases (author's transl)]. / Il comedocarcinoma della mammella. Valutazione mammografica e termografica di 52 casi.

A series of 52 patients with comedocarcinoma of the breast was studied by means of mammography and thermography. All the patients underwent surgery and histologic examination. The results stress the importance of these investigations which reach a diagnostic accuracy in 98% of the cases.

[Current role of conventional tomography in the staging of pulmonary neoplasms. Reflections based on the comparison of tomography-magnetic resonance in 81 cases]. / Ruolo attuale della tomografia tradizionale nella stadiazione delle neoplasie polmonari. Riflessioni sulla base del confronto tomografia-risonanza magnetica in 81 casi.

The preoperative conventional tomographic and Magnetic Resonance images were reviewed of 81 patients affected with bronchogenic carcinoma; all patients underwent surgery 1986 to 1988. Radiological findings were compared with surgical and pathological results to evaluate the actual role of conventional tomography in the staging of bronchogenic carcinoma. MR Imaging proved to be more useful in the evaluation of mediastinal and hilar lymph nodes. As for mediastinal node status, conventional tomography had 23.5% sensitivity, 90.6% specificity, and 76.5% overall accuracy; MR Imaging had 82.3% sensitivity, 84.4% specificity, and 84% overall accuracy. As for hilar adenopathies, tomographic sensitivity, specificity and overall accuracy were 53.3%, 72.5%, and 65.4% versus 50%, 82.3% and 70.4% with MR Imaging. Tomography was slightly superior in identifying the primary tumor (97.5% versus 92.6% for MR), as well as in the demonstration of central bronchial involvement (100% for conventional tomography versus 50% for MR Imaging). Conventional tomography is useful as a complementary technique to MR Imaging in the preoperative staging of bronchogenic carcinoma when information on central bronchial involvement is needed.

[Radiodiagnosis of thymomas]. / Contributo alla radiodiagnostica dei timomi.

On the ground of the clinical experience gained on thymomas observed during the last decade and controlled by histopathology at the National Cancer Institute of Milan, the authors report and describe the typical morphology of the above neoplasms, which were studied with both the conventional and the most advanced imaging procedures. First of all, the authors point out the common problems of differential diagnosis with other lesions in the anterior mediastinum, with a special emphasis on lymphomas. Attention is also drawn to both the diagnostic and therapeutic value of conventional radiotomographic procedures combined with CT and MRI: in particular, the former can provide an extremely valuable diagnostic support to fine needle biopsy. In the authors' opinion, explorative surgery--e.g. mediastinal endoscopy-is immediately advisable when an unquestionable diagnosis is not reached even after a most rational combination of the different imaging procedures.

[Role of teletermography in the diagnosis of primary tumors of soft tissues and bones]. / Il ruolo della teletermografia nella diagnosi dei tumori primitivi delle parti molli e dello scheletro.

The thermographic behaviour of bone and soft tissue tumors (168 malignant), submitted to this examination from 1971 to 1981, has been retrospectively analyzed and statistically evaluated. In the group of malignant neoplasms, thermography reached a good sensitivity (81.5%), a little better (but not significantly) in soft tissue tumors. Mainly three pathological features have been analyzed: histological type, size and site of neoplastic masses. None of them appears to be related with the result of thermographic examination. The authors emphasize (also from a possible prognostic point of view) the peculiar behaviour of Ewing's sarcoma, whose tendency to uniform distribution through the different thermographic classes cannot be currently explained.

[Thermography in the follow-up of bone and soft tissue tumors]. / La termografia nel controllo a distanza dei tumori delle ossa e delle parti molli.

Thermography was used for the follow-up of 16 cases of bone tumors and of 16 cases of soft tissue tumors, after conservative treatments (surgery and/or radio- and chemio-therapy). The hyperthermia, which corresponds to the primary tumor, underwent a marked reduction during the first six months after the treatment. The thermographic picture appeared normal at the first follow-up of 12/16 bone tumors and of 9/16 soft tissue tumors. The presence of local recurrencies, at 12 months distance or more, corresponded to a new hyperthermic spot and to the increase of local vascularity. Thermography is proposed as a simple and harmless procedure for the follow-up of bone and soft tissue tumors after conservative treatments.

[Radiological examination of the colon resected for neoplastic pathology in the study of complications and recurrence of the disease]. / L'esame radiologico del colon operato per patologia neoplastica nello studio delle complicanze e delle riprese di malattia.

After resection for cancer of the large bowel, because of high incidence of recurrences, careful radiological examinations must be performed during the follow-up. From the experience of more than 1800 X-ray examinations, after large bowel surgery, the authors describe the roentgen findings, pointing out pathological changes. Roentgenographic findings are distinguished considering the interval between surgery and X-ray examinations (early surveys and late surveys) and their site (anastomosis, residual colonic loops, perivisceral tissues). The main diagnostic problem usually arises in the late surveys at the anastomosis where is often difficult to distinguish a late surgical complication from a neoplastic relapse. This diagnosis is easier by comparison with films from early postoperative examinations. If they are not available correct diagnosis is yet often possible looking for some radiological signs which are carefully described.

[X-ray diagnosis of malignant breast calcifications. (author's transl)]. / Radiodiagnostica delle calcificazioni maligne della mammella.

The authors have taken into consideration the different features of malignant breast tumor calcification. Frequent, rare and extremely rare radiological pictures will be shown and a differential diagnosis with benign micro-calcifications will be considered. A correct mammographic and xerographic technical performance is absolutely necessary to enhance the images of the smallest micro-calcifications. At last we assess the importance of a radiographic control of the surgical blocks, after conservative surgery of the breast, to assure a complete removal of microcalcifications.

[Radiography signs of non-Hodgkin lymphomas with pulmonary localization]. / Semeiotica radiografica dei linfomi non-Hodgkin a localizzazione polmonare.

The authors have examined a series of 992 patients with non-Hodgkin lymphomas treated at the National Cancer Institute of Milan from 1966 to 1977. The pulmonary parenchymal lesions were studied. The lung involvement by lymphomas is unusual and show a difficult X-ray diagnosis. A classification deriving from the experience of the various roentgenologic findings is proposed. Furthermore the most important differential diagnostic difficulties, some of which have an impossible solution even with the most recent X-ray techniques, are analized.

[Angiosarcoma of the breast: mammographic and thermographic study of 4 cases]. / Angiosarcoma della mammella: studio mammografico e termografico in quattro casi.

At Istituto Nazionale Tumori of Milan four patients with histologically proven angiosarcoma of the breast were evaluated by mammography and telethermography. This is a highly malignant rare tumor which occurs more frequently in young women. The authors outline that only 90 cases have been reported in the literature (once radiologically described in 1966) and analyze clinical and especially mammographic and thermographic signs. Radiological findings simulate those of filloiden tumors or giant fibroadenomas while thermographic patterns show a nearly generalized high hyperthermia. Therefore both methods should be associated for early diagnosis and improvement of the prognosis.

[Radiological and telethermographic diagnosis of breast lymphomas (28 cases)]. / Diagnostica radiologica e teletermografica dei linfomi mammari (28 casi).

Twenty eight patients with histologically proven primary or secondary malignant lymphoma of the breast were evaluated by mammography and telethermography between 1968 and 1980 at Istituto Nazionale Tumori of Milan. This histological type is rather unusual and poor is the radiological literature on the matter. The roentgenographic findings showed especially isolate nodes with clear-cut or irregular outline, multiple displasic lesions or diffuse inflammatory-like disease. Because of such a variety of radiological matters, diagnosis is often uncertain. No significant difference between primary or metastatic disease was seen in radiological patterns of non-Hodgkin lymphomas. In the three cases of Hodgkin's lymphoma radiological findings suggested inflammatory disease. Telethermography was usefully associated showing, in the majority of cases, high hyperthermia also in "benign" mammographic patterns.

[The value of mammography in 1203 breast cancers (author's transl)]. / Validità della mammografia in 1203 casi di tumore maligno.

The value of clinical mammography is reviewed on 1203 consecutive cases of histologically proven breast malignancies examined from 1971 to 1978 at the Istituto Nazionale Tumori, Milan, and at the Radiological Department, University of Milan. The diagnostic effectiveness of mammography in this case-list corresponds to approximately 80%: the influences of the histotype and of the tumor's size on these results are reviewed and discussed. The main radiographic signs of malignancy are presented and their importance in reaching a correct diagnosis is outlined. The advantages and drawbacks of mammography are discussed and, amongst these latter, emphasis is given to structurally dense breasts as an intrinsic factor limiting the effectiveness of mammography.