Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies.

BACKGROUND: Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation. AIM: To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies. MATERIALS AND METHODS: 315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs. RESULTS: Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree. DISCUSSION: Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.

[Gastrointestinal stromal tumors]. / I tumori stromali gastrointestinali.

Gastrointestinal stromal tumors (GIST) are generally found in the stomach or small intestine and less commonly in the colon or rectum. Complete surgical removal remains the best current therapy for GISTs. The treatment of advanced GIST patients is with imatinib, a selective tyrosine kinase inhibitor. In our series, 23 patients observed between 1994 and 2004 and affected by GIST were treated with complete negative margin resections (three cases by laparoscopy).

[Retroperitoneal liposarcoma]. / I liposarcomi retroperitoneali.

Liposarcoma is the most frequent histotype of the rare and malignant retroperitoneal tumours. This neoplasm has a remarkable tendency to recurrence after surgical excision, rarely to metastasize. Recurrence usually shows a more aggressive behaviour than primitive disease with a higher tendency to penetrate into adjacent organs. The symptomatology often appears late and the first sign is frequently a palpable abdominal mass. Preoperative study involves using CT and MRI. The surgical resection is the only tool able to modify natural history with regard to survival and local recurrence. Prognosis is severe, with a survival of 5 years, variable from 12 to 50% in the different series. A very important prognostic factor is the degree of tumour and radical surgical treatment. From 1990 to 2001, 32 operations for malignant retroperitoneal tumors were performed by our surgical unit in 19 patients; in 7 of them the tumor was a liposarcoma (4 male and 3 female). Total operations for retroperitoneal liposarcoma were 15, in 4 patients a second operation was performed for recurrence, in 3 a third operation and in 1 a fourth. Eleven cases out of 15 have undergone exeresis of sarcoma. Average survival consisted in 4 years and 2 months. Intraoperative radiotherapy, performed in 3 patients, perhaps is able to offer some advantages in relation to local control of the disease and of the survival. A possible resection of eventual recurrence justifies a early follow up with CT and MRI.

[Ultrasonography and computerized tomography in the diagnosis of gallbladder carcinoma]. / Ecografia e tomografia computerizzata nella diagnosi del carcinoma della colecisti.

The US and CT images of 40 surgical patients with histologically proved gallbladder carcinoma were retrospectively reviewed. The radiologic diagnosis was correct in 22 patients (55%). Gallbladder carcinoma patterns were: an intraluminal mass (type I) (7 patients, 17.5%), focal or diffuse wall thickening (type II) (5 patients, 12.5%) a mass replacing the gallbladder (type III) (10 patients, 25%). In 5 patients with type I or II gallbladder carcinoma, US and CT diagnosis was made easier by the presence of associated findings--i.e., liver infiltration and/or metastases, lymphadenopathy, dilated intrahepatic ducts, ascites. In 7 patients a gallbladder carcinoma was suspected in the presence of a small intraluminal mass (6 cases) or of focal wall thickening (1 case), with no stones and with dilated intrahepatic biliary ducts. In the extant 18 patients (45%) the radiologic diagnosis was: polyps (6 cases), stones with cholecystitis (11 cases) and empyema (1 case). US is the examination of choice in the diagnosis of gallbladder and biliary ducts conditions, but several diagnostic problems may arise in the differentiation from polyps and acute inflammatory disease. CT better demonstrates gastrointestinal tract invasion and lymphadenopathy, which can be a valuable finding for treatment planning.

Locally advanced breast-carcinoma - results of a multimodal therapy including alternating neoadjuvant chemotherapy, surgery and radiotherapy.

Thirty women with locally advanced breast cancer (LABC), but no evidence of distant metastases, were prospectively treated with four fixed cycles of neoadjuvant chemotherapy (CT). This regimen consisted of epidoxorubicin (Epi) alternated every 21 days with cyclophosphamide, methotrexate and 5-fluorouracil (CMF). After this induction CT, subsequent therapy was planned according to the response obtained as follows: (a) modified mastectomy with axillary dissection was performed in patients who had major objective response (complete or partial), followed by four doses of adjuvant CT and radiotherapy (RT); (b) debulking rescue surgery followed by RT and 2nd line CT with mitomycin C were given in patients with stable disease or minor response. The response rate to induction CT was 63% (19 of 30 patients) (95% confidence limits 46-80%). Overall, 43% of patients had no persistance of tumor at the end of the planned therapy. After a median follow-up time of 36 months, disease-free survival (DFS) and overall survival (OS) were 35% and 47%, respectively. The median duration of DFS was 16 + months (4-52+ months). A significantly better OS was observed in complete responders compared to the others (77% versus 23.5%; p=0.01). Compliance to treatment was high, gastrointestinal and hematological toxicities were the most common side-effects. Thus, this multimodal approach is effective in reducing primary tumor size with acceptable morbidity. Five of the 11 (45%) patients non responsive to induction CT obtained a transient local control of disease after debulking surgery, RT and mitomycin C. To assess the role of alternating non cross resistant regimens as induction therapy in LABC vs conventional schedules, phase III comparative studies are warrented.

A pharmacological rationale for neoadjuvant chemotherapy with adriamycin in locally advanced breast cancer.

Some locally advanced neoplastic diseases (i.e. head and neck cancer, breast cancer and osteogenic sarcoma), benefit from neoadjuvant chemotherapy with a resultant enhanced operability and a longer disease-free survival. The pharmacological study of the tissue distribution of adriamycin in patients affected by locally advanced breast cancer has shown a preferable tropism of the drug toward the primary tumor and axillary lymph nodes. Median concentrations of the drug in the tumor were: 9.68 micrograms/gr at 30 minutes, 8.71 micrograms/gr at 24 hours and 6.44 micrograms/gr at 48 hours. Median concentration in lymph nodes at 48 hours was 10.80 in normal and 16.62 in metastatic. Lower concentrations were found at 48 hours in the mammary gland (mean 1.72 micrograms/gr), skin (mean 0.59 micrograms/gr) and in muscle tissue (mean 1.83 micrograms/gr in normal and 2.41 micrograms/gr in metastatic). As regards acute toxicity, we observed that grade II-III leukopenia was associated with longer plasmatic T1/2 beta (3 out of 6 patients) and that grade II mucositis was related to high plasma AUC values (3 out of 6 patients). Nausea and vomiting and alopecia seem to be unrelated to plasma pharmacokinetics parameters. After a median follow-up of 36 months it is suggestive that high drug concentrations in carcinoma and in metastatic lymph nodes may be predictive of longer disease-free survival and overall survival. These data give a further rationale for the use of polychemotherapies containing adriamycin in the pre-operative treatment of locally advanced breast cancer.

[Tissue polypeptide antigen: significance and prospective use in the clinical laboratory]. / L'antigene polipeptidico tessutale: significato e prospettive di impiego nel laboratorio clinico.

Sequential determination of tissue polypeptide antigen were carried out in patients with neoplastic diseases. Blood specimens were taken before surgery and one week, one month and every months after the operation. The values obtained were compared with those of a control group of blood donors and those of a control group of healthy persons. The values obtained in control groups suggest that alcohol could cause significant increase of tissue polypeptide antigen values.