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F Rilke

Publications and source records attributed to F Rilke.

At least 37 records · Page 2Linked to original sources
PubMed1997

Non-small-cell lung carcinoma tumor growth without morphological evidence of neo-angiogenesis.

Neoplastic growth is usually dependent on blood supply, and it is commonly accepted that this is provided by the formation of new vessels. However, tumors may be able to grow without neovascularization if they find a suitable vascular bed available. We have investigated the pattern of vascularization in a series of 500 primary stage I non-small-cell lung carcinomas. Immunostaining of endothelial cells has highlighted four distinct patterns of vascularization. Three patterns (which we called basal, papillary, and diffuse) have in common the destruction of normal lung and the production of newly formed vessels and stroma. The fourth pattern, which we called alveolar or putative nonangiogenic, was observed in 16% (80/500) of the cases and is characterized by lack of parenchymal destruction and absence of both tumor associated stroma and new vessels. The only vessels present were the ones in the alveolar septa, and their presence highlighted, through the whole tumor, the lung alveoli filled up by the neoplastic cells. This observation suggests that, if an appropriate vascular bed is available, a tumor can exploit it and grows without inducing neo-angiogenesis. This could have implications for strategies aimed at inhibiting tumor growth by vascular targeting or inhibition of angiogenesis.

Biomarkers, Tumor↗
PubMed1997

Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas.

Infiltration by lymphoid cells is a common feature of many human tumors, including breast carcinomas, and the degree of infiltration has been suggested to be a measure of the host immune response. Our analyses in a series of 1919 cases of primary ductal and lobular infiltrating breast carcinomas from women with a long-term follow-up revealed: (a) a 16-17% frequency of infiltrated tumors independent of the patient's age at diagnosis; and (b) a strong positive correlation between survival rates and the presence of lymphocytes at the tumor site in patients less than 40 years of age (P = 0.0002) but no association with prognosis in patients 40 years of age or older. Multivariate analysis indicated that lymphoid infiltration is independent of other conventional prognostic factors such as nodal status and tumor size in predicting survival. Thus, a possible immune response against the tumor seems to be relevant only in women with early-onset tumors. Because the immune system is functionally maximum in younger years, declining with age, this finding might reflect a difference in the efficiency of the immune system. Alternatively, the biology of these tumors might differ, leading to a difference in immuno-genicity.

Adult↗
PubMed1996

Results of a breast-cancer-surgery trial compared with observational data from routine practice.

BACKGROUND: The strength of randomised controlled trials (RCTs) is that they allow investigators to draw reliable inferences about treatment differences; physicians can then make a choice between different options. Their weakness is that they are conducted on a set of patients who cannot be regarded as a random sample from the population that will be treated outside the trial. Observational data collected in a prospective clinical database may provide more realistic estimates. METHODS: At the Istituto Nazionale de Tumori of Milan an RCT was started in 1973 (MI1) in which Halsted mastectomy was compared with quadrantectomy plus axillary dissection and radiotherapy (QUART), a breast conserving treatment, for "early-stage" primary breast cancer. In addition, a prospective clinical database was established to collect, in standard format, information on all women undergoing breast conservation thereafter and followed up at the Institute. 1760 women were treated with QUART, 350 of them being accrued in the years 1973-80 in the context of the MI1 trial. The remaining 1408 received QUART after the MI1 trial, up to December, 1984. RESULTS: In the years after the trial, the criteria for use of QUART became more liberal. However, after adjustment for baseline characteristics, out-trial patients fared no worse than trial patients in terms of survival or distant metastasis. Out-trial patients did have a slightly higher rate of local recurrence, probably because of subtle and multiple changes in the surgical procedures since the time of the trial. INTERPRETATION: The results of QUART in out-trial patients resembled those reported from research settings. In this instance, the results of clinical trials did not exaggerate the benefits obtainable in routine practice.

Adult↗
PubMed1996

Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas.

PURPOSE: Experiments were designed to investigate the association between tumor leukocytic infiltrates with other pathologic and biologic variables in primary tumors and with prognosis, and to define the phenotype of the infiltrating leukocytes. PATIENTS AND METHODS: A retrospective series of 1,207 primary breast carcinomas was studied according to different prognostic variables, including the presence of lymphoplasmacytic infiltrate (LPI). LPI was analyzed in association with other variables and survival. Additionally, a small prospective series of surgical specimens from 75 primary breast carcinomas with infiltrating leukocytes was tested by immunohistochemistry on frozen sections to phenotypically characterize the infiltrate, using anti-CD reagents, and the tumor, using anti-c-erbB-2 oncoprotein monoclonal antibody. RESULTS: In the retrospective series, menopausal status, nodal status, tumor size, stage, grade, and p185HER2 overexpression but not LPI were found to be associated with prognosis and maintained their prognostic significance in a multivariate analysis. LPI was significantly associated with some of these independent prognostic factors, such as tumor size (P = .03), stage (P = .004), grade III carcinomas (P < .000001), and overexpression of the p185HER2 (P < .000001). In some subgroups of patients in whom LPI was found more frequently, such as grade III cases or N- and c-erbB-2-positive cases, LPI was found to be indicative of a good prognosis (P = .008 and P = .03, respectively). Phenotypic analysis of the infiltrating leukocytes revealed a preponderance of macrophages in high-grade (P = .05) or c-erbB-2-positive (P = .008) tumors, whereas T cells constituted most of the infiltrate in the other tumors. CONCLUSION: Our data demonstrate different leukocytic types in the infiltrate of breast tumors with different prognostic significance.

Antigens, CD↗
PubMed1995

Local recurrences and distant metastases after conservative breast cancer treatments: partly independent events.

BACKGROUND: Local disease recurrences are a concern in conservative breast cancer surgery, and many studies have attempted to identify risk factors for these events. It is important to distinguish local recurrences linked to increased risk of distant spread from those due to inadequate local treatment. PURPOSE: We evaluated the incidence of local and distant recurrences according to demographic, biological, and pathologic variables in a large series of women who were conservatively and uniformly treated for breast cancer, with the aim of identifying women in whom local failure is predictive for distant metastases and who are therefore candidates for aggressive systemic treatment. METHODS: Medical records of 2233 women who had been hospitalized at the Milan Cancer Institute from 1970 to 1987 were analyzed. All women received quadrantectomy and axillary lymph node dissection followed by radiotherapy for the breast. Quadrantectomy is breast-conserving removal of most of the affected quadrant by a radial incision that includes part of the skin. The end points considered were local failures (including local recurrences and new ipsilateral carcinomas) and distant metastases. Statistical analysis employed the competing risks and multiple failures approaches. RESULTS: There were 119 local recurrences, 32 new ipsilateral carcinomas, and 414 distant metastases as first events. The timing of local failures and distant metastases differed: The yearly probability for local failures was approximately 1% up to the 10th year and for distant metastases was 5% in the 2nd year and decreased progressively until the 8th year. Young age was an important risk factor, with peritumoral lymphatic invasion also predictive for local and distant recurrences. Tumor size and axillary lymph node involvement were not related to local recurrence but were important predictors of distant metastases. Extensive intraductal component was only a risk factor for local recurrence. Early (< 2 years) local failure predicted for distant metastases compared with later failure. In local failure patients, the 5-year survival rate was 69% from failure. CONCLUSIONS: Local recurrences and distant metastases are partially independent events that occur at different times; several predicting factors also differ. However, women with local recurrences have increased risk of distant metastases. In particular, women 35 years old or younger at first diagnosis who had initial peritumoral lymphatic invasion and local recurrence within 2 years are at high risk for distant spread. For recurrence in cases with an extensive intraductal component or where initial local surgery was possibly inadequate, women are at lower risk.

Adult↗
PubMed1995

Analysis of estrogen and progesterone receptors on preoperative fine-needle aspirates.

For 56 cases of carcinoma of the breast, results of the immunocytochemical assay for estrogen and progesterone receptors performed on preoperative fine-needle aspirates were compared with those obtained on scraping material from the same tumors. The value and usefulness of this last analysis was demonstrated in a previous study. The level of agreement between the two cytological techniques was assessed by the k statistic. A high level of agreement was found, with k values of 0.909 and 0.889 for estrogen and progesterone receptors, respectively. The results reported here revealed the reliability of steroid receptor determination on fine-needle aspiration biopsies, provided that sufficient cellularity was available. This technique can replace the open biopsy procedure, in as much as it represents a rapid, almost painless, and easily repeated method for the assessment of the receptor status, and is useful for treatment decisions at any time during the course of the disease.

Biopsy, Needle↗
PubMed1995

Breast conservation is a safe method in patients with small cancer of the breast. Long-term results of three randomised trials on 1,973 patients.

Breast conservation has become well-established in the treatment of early mammary carcinoma. However, a standardised treatment modality has not emerged. We have analysed the data from 1,973 patients treated in three consecutive randomised trials by four different radiosurgical procedures: Halsted mastectomy, quadrantectomy plus radiotherapy, lumpectomy plus radiotherapy, and quadrantectomy without radiotherapy, to compare the outcomes of these procedures in terms of local recurrence rate and overall survival. Eligibility criteria were similar in the three trials, and comparability between the four subgroups was excellent. Median follow-up for all patients was 82 months. The annual rates of local recurrence varied markedly according to the treatment. Patients treated with Halsted mastectomy and quadrantectomy plus radiotherapy had low annual rates of local recurrence (0.20 and 0.46, respectively) while both lumpectomy plus radiotherapy and quadrantectomy without radiotherapy had significantly higher rates (2.45 and 3.28, respectively). Patients under 45 years of age had a much higher incidence of local recurrences, while in women over 55 years local recurrences were much less frequent. Overall survival curves were identical in the four groups of patients, so that the three breast conserving radiosurgical procedures had the same survival rates as Halsted mastectomy. However, local recurrence rates were markedly influenced by the treatment method, patient age and specific histological features.

Adult↗
PubMed1995

Conservation surgery after primary chemotherapy in large carcinomas of the breast.

OBJECTIVE: The authors evaluated the utility of preoperative chemotherapy in patients with large size breast carcinoma, with a view to rendering a conservative surgical approach possible or easier. SUMMARY BACKGROUND DATA: Two hundred twenty-six of 227 patients with breast cancer involving a tumor larger than 3 cm at greatest dimension were candidates for mastectomy. They were treated with various primary preoperative chemotherapies and evaluated for surgery. METHODS: After administering various chemotherapeutic regimens, the authors reevaluated the patients' conditions clinically and radiologically to plan definitive surgical treatment. If the tumor diameter was sufficiently reduced, quadrantectomy was planned; otherwise, mastectomy was performed. Complete axillary lymph node dissection was done in all cases. RESULTS: In 90% of the cases, the size reduction was sufficient to justify breast conservation; in 10%, tumor size did not decrease enough or increased, thus mastectomy was performed. In 11.8% of the cases, the tumor was no longer identifiable at surgical inspection, and in 3.5% no tumor was found on microscopic examination. Axillary lymph nodes were free of metastases in 39% of cases. Twelve local recurrences occurred among the 203 patients treated with breast conservation (5.9%) and five among the 23 patients treated with mastectomy (21.7%). CONCLUSIONS: Primary chemotherapy can expand the indication for breast conservation to large tumors; careful attention, however, must be paid to surgical technique. The position of the tumor should be marked with tattoo points on the skin before chemotherapy. The macroscopic extent of the tumor regression must be evaluated carefully, and multiple frozen section biopsies may be needed. The margins of the resected breast should be evaluated microscopically. All microcalcifications present before treatment must be resected. The skin incision and mammary resection must fulfill criteria of radicality as well as good cosmetic outcome.

Breast Neoplasms↗
PubMed1995

Papillomavirus, p53 alteration, and primary carcinoma of the vulva.

Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.

Adult↗
PubMed1995

Acral-lentiginous naevus of plantar skin.

In a consecutive series of 165 plantar naevi, a group of 36 benign naevi with sufficiently distinctive histopathological features to justify their classification as a special entity, here designated acral-lentiginous naevus, was identified. The main morphological features distinguishing the acral-lentiginous naevi from other acral non-lentiginous naevi are: elongation of rete ridges, continuous proliferation of melanocytes at the dermo-epidermal junction, presence of single scattered melanocytes, or less commonly small clusters, within the upper epidermis, poor or absent lateral circumscription, melanocytes with abundant pale cytoplasm and round to oval, sometimes hyperchromatic, nuclei and prominent nucleoli present at the dermo-epidermal junction. Some histological features of acral-lentiginous naevi are similar to those of dysplastic naevi: however, anastomosing rete ridges, cytological atypia and well-formed lamellar fibroplasia are absent. The histopathological criteria to distinguish these naevi from melanoma are: the lack of pagetoid lateral spread, the absence of mitotic activity in the deep dermal component and the evidence of dermal naevocytic differentiation. The identification of this benign acral naevus, that we have identified as the benign counterpart of acral lentiginous melanoma, is important in order to avoid misdiagnoses and consequent under- or over-treatment of doubtful pigmented lesions of acral skin.

Diagnosis, Differential↗
PubMed1995

Proprotein convertases (PC1/PC3 and PC2) in normal and neoplastic human tissues: their use as markers of neuroendocrine differentiation.

By immunocytochemistry and immunoblotting, we examined normal and neoplastic human tissues with polyclonal antibodies raised against selected peptide regions of proprotein convertase-2 and -3 (PC2 and PC3), two proteases that have been shown to selectively cleave neuroendocrine precursor molecules at pairs of basic residues. Immunoreactivity for both enzymes was detected in neuroendocrine cells of pituitary, gut, pancreas, thyroid, and adrenals and in tumors thereof, but was absent in thyroid follicular cells, parathyroids, adrenal cortex, testes, and a number of nonneuroendocrine tissues, both normal and tumorous. Although both PCs were virtually universal concomitants of the neuroendocrine system, cells with a neural phenotype (e.g. pheochromocytes and Merkel cells) predominantly contained PC2, whereas classic endocrine cells contained mostly PC3. PC3 immunoreactive cells were abundant all along the gastrointestinal tract, whereas PC2 was highly expressed only in the pyloric antrum and proximal third of duodenum. Double immunostaining experiments revealed colocalization of PC3 with virtually all gastrointestinal peptides, whereas PC2 immunoreactivity was mostly expressed in gastrin, cholecystokinin, and somatostatin cells. Noticeably, the proportion of glucagon-producing cells immunoreactive for PC3 was high in the gut and low in pancreatic islets and glucagonomas, whereas the reverse occurred for PC2. At the ultrastructural level, immunostaining was confined to the mature dense core granules, the site of storage of granins and peptide hormones. With the exception of parathyroid cells, PC2 and/or PC3 expression correlated with the occurrence of granins, canonical markers of the secretory granules. Immunoblotting experiments confirmed the identity of the immunocytochemical reactivities. It is concluded that PC2 and PC3 are highly sensitive markers of neuroendocrine differentiation and have distinct distribution patterns, and that antibodies to these enzymes may play an important role in the analysis of tumors.

Aspartic Acid Endopeptidases↗
PubMed1995

Poorly differentiated forms of papillary thyroid carcinoma: distinctive entities or morphological patterns?

The concept that poorly differentiated carcinomas (PDC) represent a group in an intermediate position in the spectrum of follicular cell-derived carcinomas of the thyroid gland is currently well established. Because at the well-differentiated end of the spectrum there are two groups of entities with distinct biological characteristics, ie, the papillary carcinoma (PC) and the follicular carcinoma (FC), we examined the group represented by PCs to ascertain whether papillary carcinoma-related PDCs (pPDC) represent merely a histologic variant or a distinct pathologic entity. For this purpose 227 consecutive PCs were reclassified according to current criteria. The association between the presence of a tumoral pattern consistent with pPDC (response variable), and prognostic factors such as gender age, pTNM (predictive variables) was evaluated in terms of odds ratio statistics. One hundred eighty-three of 227 cases, defined as PCs met the World Health Organization criteria of the not otherwise specified (NOS) (79 cases), microcarcinoma (65 cases), encapsulated (4 cases) and follicular (35 cases) variants. Forty-four cases, defined as pPDCs, met those of the tall cell (39 cases), columnar cell PC (2 cases) and mixed tall cell-columnar cell PC (3 cases) variants. Statistical analyses of the two groups of patients showed a significant correlation between differentiation and age above 40 years, extrathyroid tumor extension and low ratio of regional nodal involvement at the onset of disease. More strikingly they also showed that morphology, ie, a tumoral pattern consistent with pPDC (differentiation), is the strongest predictor of biological behavior including recurrences and recurrence-related deaths that appear to occur five and twenty times more frequently in pPDCs than in PCs, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

The Bcl-2 protein: a prognostic indicator strongly related to p53 protein in lymph node-negative breast cancer patients.

BACKGROUND: The bcl-2 gene (also known as BCL2) encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. The protein has been detected by immunohistochemical procedures in hormonally regulated epithelia. PURPOSE: We analyzed the predictive relevance of Bcl-2 expression on 6-year relapse-free and overall survival in lymph node-negative breast cancers in relation to pathologic (tumor size) and biologic ([3H]thymidine-labeling index, p53 protein expression, and estrogen receptor [ER] status) features. METHODS: The expression of Bcl-2 and p53 was detected by immunohistochemistry on paraffin-embedded sections from 283 node-negative resectable breast cancers treated with local-regional therapy alone until relapse. The [3H]thymidine-labeling index was evaluated on histologic sections after incubation of fresh tumor tissue with [3H]thymidine, and ER content was determined by the dextran-coated charcoal absorption technique. RESULTS: A significantly higher fraction of Bcl-2-positive cells was observed in small, ER-positive, slowly proliferating, and p53-negative tumors than in large, ER-negative, rapidly proliferating, and p53-positive tumors. A stronger association was observed between Bcl-2 and p53 expression than between these variables and [3H]thymidine-labeling index. In univariate analysis, Bcl-2 and p53 expression, [3H]thymidine-labeling index, tumor size, and ER status were indicators for relapse-free and, with the exception of tumor size, overall survival within 6 years of surgery. In multivariate analysis, Bcl-2 failed to maintain its prognostic role for relapse-free and overall survival in the presence of p53 expression, whereas the [3H]thymidine-labeling index was still statistically significant as a predictor for both events. CONCLUSION: The predictive role of Bcl-2 expression on 6-year relapse-free and overall survival was mainly dependent on p53 expression.

Breast Neoplasms↗
PubMed1994

Bcl-2 protein expression in carcinomas originating from the follicular epithelium of the thyroid gland.

The bcl-2 product has been related to the block of programmed cell death (apoptosis) both in lymphoid and in epithelial cells. The pathological expression of bcl-2 has been investigated mainly in haematological malignancies. Here we have investigated bcl-2 expression in a model of epithelial tumours represented by the spectrum of carcinomas arising from the follicular epithelium of the human thyroid gland. The analysis was carried out by immunocytochemistry on archival material using monoclonal antibodies against bcl-2 and thyroglobulin (Tg) on consecutive sections of 94 well-differentiated carcinomas (WDCs), 19 poorly differentiated carcinomas (PDCs), and 22 undifferentiated carcinomas (UCs) of the thyroid gland. In a subset of 5 cases of UC showing a differentiated component (UC-D), the expression of p53 protein was also investigated. As controls, fetal and adult normal thyroid glands and adenomas were analysed. bcl-2 expression was detected in 74 of 94 cases (78.7 per cent) of WDC, 16 of 19 cases (84.2 per cent) of PDC, and 3 of 22 cases (13.6 per cent) of UC. Simultaneous expression of bcl-2 protein and Tg was observed in 74 of 94 cases (78.7 per cent) of WDC, 13 of 19 cases (68.4 per cent) of PDC, and in no case of UC. bcl-2 and Tg immunostaining was detected in all fetal and normal thyroid glands as well as in the adenoma specimens examined. In the subset of UC-D, mutual exclusion of bcl-2 and p53 expression was observed in the undifferentiated and differentiated components (p53 but not bcl-2 expressed in the former).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗