Effect of adjuvant trastuzumab treatment in conventional clinical setting: an observational retrospective multicenter Italian study.

Clinical trials have shown the efficacy of trastuzumab-based adjuvant therapy in HER2-positive breast cancers, but routine clinical use awaits evaluation of compliance, safety, and effectiveness. Adjuvant trastuzumab-based therapy in routine clinical use was evaluated in the retrospective study GHEA, recording 1,002 patients treated according to the HERA protocol between March 2005 and December 2009 in 42 Italian oncology departments; 874 (87.23 %) patients completed 1-year trastuzumab treatment. In 128 patients (12.77 %), trastuzumab was withdrawn due to cardiac or non-cardiac toxicity (28 and 29 patients, respectively), disease progression (5 patients) or the clinician's decision (66 patients). In addition, 156 patients experienced minor non-cardiac toxicities; 10 and 44 patients showed CHF and decreased LVEF, respectively, at the end of treatment. Compliance and safety of adjuvant trastuzumab-based therapy in Italian hospitals were high and close to those reported in the HERA trial. With a median follow-up of 32 months, 107 breast cancer relapses were recorded (overall frequency, 10.67 %), and lymph node involvement, estrogen receptor negativity, lymphoid infiltration, and vascular invasion were identified as independent prognostic factors for tumor recurrence, indicating that relapses were associated with advanced tumor stage. Analysis of site and frequency of distant metastases showed that bone metastases were significantly more frequent during or immediately after trastuzumab (<18 months from the start of treatment) compared to recurrences in bone after the end of treatment and wash-out of the drug (>18 months from the start of treatment) (35.89 vs. 14.28 %, p = 0.0240); no significant differences were observed in recurrences in the other recorded body sites, raising the possibility that the protection exerted by trastuzumab is lower in bone metastases.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

Role of hormonal risk factors in HER2-positive breast carcinomas.

Examination of parity, age at menarche and at menopause by HER2 status in a large series of breast carcinomas showed a statistically significant increased-frequency of HER2-positive tumours in lower risk subgroups. The findings suggest a difference in the protective role of hormone-related risk factors between HER2-positive and -negative tumours.

Effect of long-term adjuvant therapy with interferon alpha-2a in patients with regional node metastases from cutaneous melanoma: a randomised trial.

BACKGROUND: Less than half of patients with melanoma that has spread to local draining regional lymph nodes (stage III melanoma) live with no disease for 5 years or longer after surgery. We aimed to see whether interferon alpha-2a increased survival prospects in these patients. METHODS: 444 patients from 23 centres in the WHO Melanoma Programme had complete lymphadenectomy for pathologically proven regional nodal spread of melanoma and were randomly assigned to receive either 3 MU subcutaneously of recombinant interferon alpha-2a three times a week for 3 years, or to observation alone after surgery. Patients were stratified by centre, nodes with macroscopic or microscopic melanoma, number of affected nodes, and nodal metastatic spread. Treatment was continued for 3 years or until first sign of relapse. FINDINGS: 424 patients entered the study. 5-year disease-free survival of those who had surgery plus interferon alpha-2a was 27.5% (95% CI 21.7-33.6); for those who received surgery alone, survival was 28.4% (22.5-34.6) (p=0.50). Neither Kaplan-Meier cumulative survival rates, nor multivariate analysis of survival, showed a difference between those who had surgery and interferon alpha-2a (35%, 95% CI 29-42) and those who had surgery alone (37%, 31-44). INTERPRETATION: Patients with melanoma that has spread to the local draining regional lymph nodes tolerate well 3 MU of interferon alpha-2a given subcutaneously three times a week for 3 years, but this treatment does not improve either disease-free or overall survival.

Thromboembolic risk in atrial flutter. The FLASIEC (FLutter Atriale Società Italiana di Ecografia Cardiovascolare) multicentre study.

AIMS: Patients with atrial flutter are believed to be at lower risk of thromboembolism than patients with atrial fibrillation. However, the incidence of atrial thrombi and the need for anticoagulation in patients with atrial flutter is not well established. METHODS AND RESULTS: A prospective observational multicentre study was undertaken to assess the frequency of atrial thrombi and spontaneous echocontrast and the prevalence for aortic complex atherosclerotic lesions in a cohort of unselected patients with atrial flutter. We evaluated 134 patients (102 male, aged 70+/-9 years); exclusion criteria were history of atrial fibrillation, rheumatic mitral valve disease and mitral mechanical prosthesis. The median of atrial flutter duration was 33 days. Twelve patients had been taking warfarin for more than 7 days. One hundred and twenty-four patients (94%) underwent a transoesophageal echocardiogram, which revealed left atrial appendage thrombi in two patients (1.6%) and right atrial thrombi in one patient (1%). At least moderate left atrial echocontrast was found in 16/124 patients (13%). Complex atherosclerotic aortic plaques were detected in 10 patients (8%). Atrial flutter conversion was attempted in 93/134 patients (69%). At the 1-month follow-up, two patients experienced a thromboembolic event following restoration of sinus rhythm. CONCLUSIONS: Atrial thrombi and echocontrast, and complex aortic atherosclerotic plaques are relatively uncommon in patients with atrial flutter. Post-cardioversion embolism was observed in two patients in our study population.

Percutaneous transluminal coronary revascularization in women: higher risk of dissection and need for stenting.

BACKGROUND: Even though success rates of percutaneous transluminal coronary angioplasty (PTCA) are influenced by gender, women are at higher risk for adverse procedural events. Plaque dissection has been demonstrated to cause more adverse cardiac events during PTCA in the female gender than the male, but it is not clear how much it could influence stent implantation and procedural complications in the stent era. This study sought to evaluate whether the prevalence of dissection is equal in men and women with similar vessel size, which factors are associated with the risk of this complication and whether stenting has modified the immediate outcome. METHODS: Three hundred thirty-nine lesions were studied in 100 consecutive women and 128 men with a vessel diameter < or = 3.5 mm, who underwent PTCA in our catheterization laboratory between March 1998 and March 1999. RESULTS: Procedural success rates were similar in the two groups (93.9% women vs 97.6% men). Complications were one coronary artery bypass graft and five acute myocardial infarctions. In the group of women, however, there was a significant increase in the incidence of plaque dissection during the procedure (37.9 vs 21.7%, p = 0.001), with consequent increased need for stenting (70.4 vs 52.2%, p < 0.05) to achieve adequate final results. Moreover, dissection was strongly associated (p = 0.03) with procedural complications. Multivariate analysis of the whole patient cohort showed the risk of dissection to be associated only with the female gender (p = 0.009), diabetes (p = 0.029), and type C lesion morphology (p = 0.019). CONCLUSIONS: Women are at higher risk of plaque dissection, which is associated with adverse procedural events and an increased need for stenting.

Multi-institutional phase II randomized trial of integrated therapy with cisplatin, dacarbazine, vindesine, subcutaneous interleukin-2, interferon alpha2a and tamoxifen in metastatic melanoma. BREMIM (Biological Response Modifiers in Melanoma).

The aim of this study was to evaluate the toxicity and efficacy of a monochemotherapy regimen of dacarbazine (DTIC), tamoxifen , interferon-alpha2a and interleukin-2 (IL-2) and two polychemotherapy regimens of cisplatin, DTIC, vindesine, tamoxifen, interferon-alpha2a with or without IL-2 in patients with metastatic melanoma. Consecutive patients with metastatic melanoma were enrolled in this trial and were randomized to arm A, consisting of DTIC 800 mg/m2 every 21 days, IL-2 9 MIU subcutaneously days 1-5 and 8-12, arm B, consisting of cisplatin 30 mg/m2 days 1-3, DTIC 250 mg/m2 days 1-3 and vindesine 2.5 mg/m2 day 1 every 28 days (CVD), or arm C, consisting of CVD plus IL-2 6 MIU days 1-5 and 8-12 every 28 days. In all three arms Interferon 3 MU subcutaneously three times a week and tamoxifen 20 mg orally were given throughout. Ninety-two patients were included in this study. Patient characteristics in the three groups were well balanced. The three regimens were delivered on an outpatient basis without major toxicity. The toxicities that did occur consisted primarily of flu-like symptoms in the IL-2 arms (A and C) and haematological toxicities in the CVD arms (B and C). No grade IV toxicities were encountered and no treatment-related deaths occurred. The total response rate was 13% in arm A, 35% in arm B and 37% in arm C. The median duration of response was 6 months and the median survival was 11 months. According to this phase II randomized trial polychemoimmunotherapy with CVD has an objective response rate of 35-36%, while monochemoimmunotherapy with DTIC has a response rate of 13%.

Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors.

Many different pathological and biological variables which characterize breast carcinomas have been found to be associated. The aim of this work was to analyze the complex relationship among these parameters. The pathologic, biologic, and clinical characteristics of a series of primary breast carcinomas from 676 patients were retrospectively investigated. Multiple correspondence analysis of 13 factors revealed clustering of eight pathobiologic variables, that is histologic grade, necrosis, lymphoid infiltration, number of mitoses, c-erbB-2 overexpression, p53, progesterone receptor, and bcl2 expression. An index for each tumor calculated on the basis of these eight factors served to distinguish two different tumor phenotypes, designated A and B. Phenotype A is represented by tumors sharing most of the biologic features of normal breast tissues: indeed, these tumors are characterized by a relatively high degree of differentiation, low proliferation, no necrosis or leukocyte infiltration, and no gene alterations. By contrast, phenotype B is quite divergent from the normal tissue because of its poor differentiation, high proliferation, frequent gene alterations and evidence of a host immune reaction. As regards the disease progression, these two subsets showed marked differences: phenotype A tumors had a low recurrence rate per year that remained constant over time and affected more frequently elderly patients, whereas group B tumors showed high aggressivity in the first years after surgery followed by a low long-term recurrence rate and were more frequently seen in younger patients. These data suggest that breast carcinoma consists of two different subsets that can be identified on the basis of pathobiologic features.

Dose-escalation of CHOP in non-Hodgkin's lymphoma.

BACKGROUND: CHOP is considered to be the gold standard for patients with histologically aggressive non-Hodgkin's lymphoma both in limited and advanced stages. In order to determine the maximum tolerable dose of an intensified CHOP regimen, a dose-escalation study of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with non-Hodgkin's lymphoma (NHL) was started. PATIENTS AND METHODS: With an increased fixed dose of doxorubicin at 75 mg/m2 instead of 50 mg/m2 on day 1 and standard doses of vincristine (1.4 mg/m2 on day 1) and prednisone (100 mg day 1 through 5), cyclophosphamide dose was escalated by increments of 250 mg/m2 in consecutive cohorts of at least three patients starting from 1000 mg/m2. Granulocyte-colony stimulating factor (G-CSF) support was added to the regimen starting from the dose-level inducing grade 4 neutropenia lasting more than five days in two patients. Dose limiting toxicity was defined as either the dose inducing grade 4 neutropenia lasting more than seven days despite the use of G-CSF, or grade 3-4 thrombocytopenia lasting more than seven days, or any grade 4 non-hematological toxicity other than alopecia. The dose-level below the one inducing dose-limiting toxicity was defined as maximum tolerable dose. All patients were treated on an outpatient basis. Dose-intensity parameters for single agent doxorubicin and cyclophosphamide as well as for the whole regimen were evaluated. RESULTS: Eighty-seven patients are evaluable over a four-year study period. At 1750 mg/m2 dose-level, G-CSF was added to the regimen according to described criteria. At the cyclophosphamide dose of 3000 mg/m2, dose-limiting hematological toxicity occurred in two patients, with one grade 4 thrombocytopenia and neutropenia and one grade 4 neutropenia lasting more than seven days. Thus, cyclophosphamide dose of 2750 mg/m2 was defined as maximum tolerable dose. CONCLUSIONS: CHOP intensification of approximately 1.8 times that of the standard regimen is feasible and safely administered on an outpatient basis with G-CSF support. Further investigation on the role of dose-intensity in the outcome of NHL should focus on the comparison of intensified CHOP regimen and standard CHOP or high-dose chemotherapy.

Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis.

PURPOSE: This study was designed to evaluate the frequency of microscopic distal intramural spread in rectal adenocarcinoma and its correlation to other histopathologic prognostic factors. METHODS: We examined 55 patients with adenocarcinomas of the lower one-third of the rectum and measured the extent of distal intramural spread in the submucosa and/or muscular layer in comparison with Dukes Stage, diameter of tumor, distance of distal margin of resection from tumor, depth of infiltration into perirectal adipose tissue, nodal status, neoplastic infiltration of lymphatic vessels, blood vessels, and nervous branches. RESULTS: Distal intramural spread was found in 40 percent of patients, 77 percent of whom had advanced tumors with nodal metastases. Distal intramural spread appeared to be strictly related to tumor size (superior to 40 mm), infiltration of the perirectal adipose tissue, multiple positive lymph nodes, presence of neoplastic emboli in the intramural lymphatic vessels, and neoplastic invasion of the nervous branches. Local recurrence occurred in one Dukes Stage B patient with a positive distal margin of resection and in four patients with a negative distal margin of resection: three Dukes Stage C and one Dukes Stage B patients with neoplastic involvement of the circumferential margin of resection of the mesorectum. CONCLUSION: These preliminary data suggest that distal intramural spread may carry little importance in determining local recurrence of rectal adenocarcinoma.

Laminin activates the p185HER2 oncoprotein and mediates growth inhibition of breast carcinoma cells.

The interaction between laminin and the oncoprotein encoded by the c-erbB-2 oncogene was studied in vitro and in vivo in human breast carcinomas. In vitro analysis of breast carcinoma cell lines overexpressing p185HER2 revealed that laminin, but not fibronectin, induced tyrosine phosphorylation and down-modulation of oncoprotein membrane expression. Laminin also specifically inhibited growth of p185HER2-positive cell lines. No direct binding between the recombinant extracellular domain of p185HER2 and laminin was found. Induction of oncoprotein down-modulation by anti-integrin antibodies and coprecipitation of the oncoprotein with the beta 4 integrin subunit indicate that the interaction between p185HER2 and laminin occurs through integrin molecules. The relevance of this in vitro observation was verified in vivo by analysing the prognostic value of p185HER2 overexpression as a function of laminin production on archival paraffin-embedded sections of 887 primary breast tumours. The results revealed an association between p185HER2 overexpression and unfavourable prognosis in tumours negative for laminin production, whereas in laminin-producing tumours, the oncoprotein overexpression was not associated with tumour aggressiveness.

Expression of bone sialoprotein in primary human breast cancer is associated with poor survival.

We have recently demonstrated that bone sialoprotein (BSP), a bone-matrix protein involved in hydroxyapatite crystal formation, is ectopically expressed in human breast cancers. We explored a possible association between expression of BSP in primary breast cancer and patients' survival. We analyzed BSP expression in 454 breast-cancer patients by immunohistochemistry on archival paraffin-embedded material using an anti-BSP polyclonal antibody. BSP expression was correlated to survival, tumor size, axillary lymph-node status and first site of distant metastasis. Of the breast cancers analyzed, 89% expressed detectable amounts of BSP. We found a statistical association between expression of BSP and poor prognosis as indicated by survival curves analyzed using the log rank and the Gehan methods. BSP expression was significantly higher in breast-cancer patients with axillary lymph-node involvement. Interestingly, survival of patients with positive lymph nodes but BSP-negative tumors was significantly higher than that of patients with no lymph-node involvement but BSP-positive cancers. The frequency of bone metastases was higher in the group of patients with BSP-positive tumors (22%) than in the group with BSP-negative cancers (7%). There was a significant increase in the incidence of lung metastases in patients whose tumors were negative for BSP. Our data show that bone sialoprotein expression in breast cancer is associated with poor prognosis. BSP detection also appears to be a valuable marker with which to identify, among the lymph-node-negative patients, those who have high risk of disease progression.

Total rectal resection, mesorectum excision, and coloendoanal anastomosis: a therapeutic option for the treatment of low rectal cancer.

BACKGROUND: There is recent and sporadic evidence indicating that patients with very low rectal cancer may be treated via a sphincter-saving procedure, obviating the need for abdominoperineal resection and definitive colostomy. This study confirms these findings. METHODS: From March 1990 to October 1994, 79 patients affected with primary low rectal cancers were submitted for total rectal resection, mesorectum excision, and coloendoanal anastomosis. All lesions were located within 8 cm of the anal verge (within 6 cm in 64 cases). RESULTS: Eight patients relapsed at the pelvic level, and one patient only at the paraanastomotic site. Postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 66% of cases after colostomy closure, and many patients (63%) had one or two bowel movements a day. Sixty-two patients of this series are alive, 49 without actual evidence of disease. Follow-up ranged from 2 to 56 months (median 23). CONCLUSIONS: The clinical and pathological data derived from this study suggest that radical mesorectum excision more than a large clearance margin of resection remains the most important factor in reducing the incidence of local relapse after low rectal cancer surgery and that total rectal resection and coloendoanal anastomosis is a suitable and safe option to traditional, demolitive surgical techniques.

Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma.

BACKGROUND: Primary cutaneous melanoma is often infiltrated lymphocytes that provide the opportunity to study what may be the local immunologic reaction to the tumor and to correlate the presence of these lymphocytes with overall survival. In an attempt to delineate the histologic diagnostic criteria, to classify different categories of lymphocytic infiltrates, previously described by Elder et al. at brisk, nonbrisk, and absent, and to verify their prognostic significance, we reviewed 285 consecutive cases of primary cutaneous melanomas (American Joint Committee on Cancer Stage I and II). METHODS: In addition to clinical variables (age, sex, and location of tumor) and the presence of tumor infiltrating lymphocytes in the vertical growth phase, the histopathologic attributes reviewed included mitotic rate, thickness, and regression. The results were derived from independent histopathologic review by two pathologists (C.G.C., M.C.M., Jr.) on separate occasions. A multivariate analysis of survival was performed with the Cox's regression model. RESULTS: The 5- and 10-year rates for melanoma with a vertical growth phase and a brisk infiltrate were 77% and 55%, respectively. For tumors with a nonbrisk infiltrate, the 5- and 10-year survival rates were 53% and 45%, respectively, and for tumors with absent tumor infiltrating lymphocytes, the 5- and 10-year survival rates were 37% and 27%, respectively. Mitotic index, thickness, and tumor infiltrating lymphocytes were statistically (univariate analysis) significant prognostic factors (P = 0.003, 0.000001, 0.0003, respectively), whereas the presence or absence of regression is not. In the univariate statistical analysis, the sex of patients and site of melanoma also were statistically significant (P = 0.00001 and 0.002 respectively), whereas age (P = 0.98) was not statistically significant. The multivariate analysis of thickness, mitotic rate, and tumor infiltrating lymphocytes showed that thickness and presence tumor infiltrating lymphocytes were significant and independent histologic prognostic factors. With regard to the clinical factors, sex retained its independent prognostic significance. The histologic characteristics of melanoma with vertical growth phase (brisk, nonbrisk, and absent) are exemplified. CONCLUSIONS: We demonstrated that when categories of tumor infiltrating lymphocytes are strictly defined, they indeed have very strong predictive value for primary cutaneous melanomas with a vertical growth phase. This work confirms the work of Clark et al. and fully illustrates the brisk, nonbrisk, and absent categories of infiltration. Finally, a multivariate analysis comparing thickness, mitotic rate and presence of tumor infiltrating lymphocytes showed that only thickness and presence of tumor infiltrating lymphocytes are significant and independent positive histologic prognostic factors.

Manual dissection of adenocarcinoma of the lower third of the rectum specimens for detection of lymph node metastases smaller than 5 mm.

BACKGROUND: The question of whether manual dissection when searching for metastatic lymph nodes from rectal cancer (less than 5 mm) is a reliable method remains controversial. METHODS: We examined 50 consecutive cases of primary adenocarcinoma of the rectum treated with a sphincter-sparing total rectum resection, total mesorectum excision, and coloanal anastomosis. We used a manual method for the detection of lymph nodes. RESULTS: One thousand seven hundred ninety-three lymph nodes were found (mean, 36 per patient). One hundred seventy-four contained metastases. Seventy-nine (45.4%) of the affected lymph nodes were less than 5 mm in greatest dimension. The percentage of metastases to small lymph nodes was similar to the percentage reported by Kotanagi (50%), but lower than the report of Herrera (78%), who used a clearing technique to search for regional lymph nodes. CONCLUSIONS: A median 17 months follow-up in these patients demonstrated that metastases in small lymph nodes are important in the accurate staging of rectal tumors and that a manual method of searching for small lymph nodes is reliable.

Biological activity and clinical efficacy of intravenous high-dose thymopentin in metastatic melanoma patients.

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1-7 months, and six remain alive with evidence of disease after a follow-up of 2-7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+ and CD4+. The CD4+ cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+ cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8+ and CD4+ lymphoid cells. The role of TP5 may be an activation of CD4+ and CD8+ lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

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.

Prognostic significance of laminin production in relation with its receptor expression in human breast carcinomas.

Laminin is a basement membrane glycoprotein whose expression has been widely related to cancer progression. Laminin production by primary breast carcinomas was investigated using immunohistochemistry on archival specimens from a retrospective series with long term follow-up. Laminin production was found to be independent of the clinical and pathological variables analyzed, whereas a statistically significant direct association with the expression of the laminin receptor and a negative association with the differentiation-related antigen Ca-MBr8 were observed. Survival analysis indicated that laminin positivity by itself has no prognostic significance. However, when analyzed together with the laminin receptor expression, laminin was associated with a good prognosis in receptor-negative tumors and with the worst prognosis in receptor-positive tumors.

Acral lentiginous melanoma. A histological type without prognostic significance.

BACKGROUND: Acral lentiginous melanoma (ALM) is reported to have a poorer prognosis than melanomas of other histotypes. OBJECTIVE: The purpose of this paper is to verify if ALMs, per se, have a more aggressive behavior or if the poorer prognosis of these patients is due to a later diagnosis. METHODS: Clinical charts of 165 patients with acrally located melanoma were reviewed as well as all histological slides. In all patients, histotype, Clark's level, Breslow thickness, pigmentation, presence of ulceration, and regression were reported. Mitotic index, vascular invasion, and microscopic satellitosis were also determined. Survival of the 64 patients with ALM was compared with survival observed in the remaining 101 acral (nonlentiginous) melanomas. RESULTS: Melanoma localized at acral sites constitute 8.9% of the 1845 patients with melanoma treated at our Institute from 1975 to 1990. All were Caucasian, 57 were males, and 108 females. Out of the 165 patients with this localization, 64 (38.8%) were classified as ALM. Disease-free and overall survival of the 64 ALM patients were not different at a statistically significant level compared with the areas observed in the other acral nonlentiginous melanoma. CONCLUSION: The survival difference between ALM and other histological types is due to a later diagnosis and not to a more aggressive behavior of ALM.

Prognosis based on primary breast carcinoma instead of pathological nodal status.

In breast cancer patients, prognostic information required to plan post-surgical therapy is obtained mainly through axillary dissection. This study was designed to establish a new prognostic score based solely on parameters of the primary tumour as an alternative to axillary surgery in assessing prognosis. Eight different prognostic factors, including menopausal status, tumour size, grading, lymphatic invasion, desmoplasia, necrosis, c-erbB-2 and laminin receptor expression, were evaluated retrospectively on a large series of primary breast carcinoma patients. From multivariate analysis, four independent parameters were selected and examined, alone and in combination, for their prognostic potential. These parameters were used to generate a prognostic score that was analysed retrospectively in 467 N0-N1a patients to determine its predictive value for survival. The score, which includes variables such as tumour size, grading, laminin receptor and c-erbB-2 overexpression, was established based on the number of negative prognostic factors: score 1 refers to cases in which all four parameters reflect a good prognosis, scores 2 and 3 refer to tumours in which, respectively, one or two of the four parameters reflect a poor prognosis, whereas score 4 refers to tumours with three or four poor prognosis factors. Analysis of the overall survival of the four score groups shows that patients with score 1 tumours (22% of the total) had the best prognosis with a 15 year survival of 82%, patients with score 2 and 3 had an intermediate prognosis, whereas score 4 patients had the poorest prognosis with a 15 year survival of only 38%. Moreover, survival in the N+ score 1 cases was found to be longer than that in the total N- patients. Our data suggest that the primary tumour score provides more reliable prognostic information than pathological nodal status, and that axillary dissection can be avoided in a large number of patients.