Relationship between tumour shrinkage and reduction in Ki67 expression after primary chemotherapy in human breast cancer.

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse.

p53 but not bcl-2 immunostaining is predictive of poor clinical complete response to primary chemotherapy in breast cancer patients.

Preoperative chemotherapy administered to breast cancer (BC) patients is a model for studying in vivo the interaction between cytotoxic treatment and clinical and biological parameters. Apoptosis induced by anticancer agents is a mechanism of treatment activity; therefore, overexpression of genes inhibiting the apoptotic pathway could produce drug resistant tumors. In the present study, the two most studied inhibitors of apoptosis, the bcl-2 gene and the mutant p53, have been evaluated to assess whether they may play a role in modulating response of BC to primary chemotherapy. From August 1990 to January 1997, 143 patients bearing T(2-4)N(0-1)M0 primary BC were submitted to two different chemotherapeutic regimens before surgery. The first 64 received the cyclophosphamide, methotrexate, 5-fluorouracil (CMF) regimen (on days 1 and 8 and every 28 days thereafter) associated with tamoxifen (30 mg daily) in case of estrogen receptor (ER)-positive BC, and the remaining 79 were submitted to single agent epirubicin (120 mg/m2 every 21 days). The expression of p53, bcl-2, Ki67, ER, progesterone receptor, c-erbB2, and the multidrug resistance P-glycoprotein (gp-170) was evaluated in BC specimens obtained at diagnosis by incision biopsy and at postchemotherapy surgery. At the end of chemotherapy administration (median, 3 cycles; range, 2-6), the clinical complete response (cCR) rate was superimposable in the patient subgroups with bcl-2-positive or -negative primary tumors; conversely, p53 expression, at a cutoff of 10% positive cells, was significantly associated with a lower cCR rate (9.4 versus 27.0%; P < 0.04). p53 was a significant predictor for poor cCR in the subset submitted to epirubicin (3.6 versus 25.5%; P < 0.02; in patients with p53+ and p53- BC, respectively); by contrast, only a trend toward lower cCR has been observed in patients with p53+ tumors receiving CMF +/- tamoxifen with respect to p53- ones. The distribution of cCR according to the gp-170-positive or -negative tumors was 8 versus 22% in patients submitted to epirubicin and 29 versus 30% in those receiving CMF +/- tamoxifen, respectively. In a multivariate regression analysis, after adjusting for treatment administered (epirubicin versus CMF +/- tamoxifen), menopausal status, tumor and node status, histology grade, ER, progesterone receptor, c-erbB2, Ki67, bcl-2, and gp-170 expression, the p53 status maintained an independent predictive role for cCR. Most of the tumors undergoing change in percentage of p53 expression after both treatments originally harbored mutant protein, and only four BC specimens that were p53 negative before chemotherapy became positive afterward. These data confirm in vivo the concept that the responsiveness of tumors to chemotherapy in part derives from the capability of BC cells to undergo apoptosis. The role of mutated p53 in preventing response is more evident in patients submitted to epirubicin, and this may be caused by the up-regulation of multidrug resistance gene expression by p53 inactivation. p53 is a stable phenotype and is not inducible by at least three or four chemotherapy cycles.

Metastasis in the chest wall and in the right ventricle from hepatocellular carcinoma. Description of a clinical case.

The ante mortem diagnosis of right ventricular metastasis from hepatocellular carcinoma (HCC) is quite rare. Also the metastatic invasion of the chest wall following a liver biopsy is seldom reported. We describe a 67 year old patient that, 30 months after a liver biopsy showing HCC, developed an isolated metastasis of the chest in the site of the biopsy which was treated by radiotherapy. The same patient, after 8 months, complained of dyspnea on effort and ECG showed signs of ischemia: echocardiogram, CT scan and MRI revealed the presence of a metastatic mass in the right ventricular cavity. Post mortem examination confirmed the diagnosis.

Cytotoxic and antiproliferative activity of the CMF regimen administered in association with tamoxifen as primary chemotherapy in breast cancer patients.

Seventy six consecutive patients with T2-4, N0-1, M0 primary breast cancer (BC) received a median of 3 cycles of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) regimen. Tamoxifen was concomitantly administered in patients with estrogen receptor positive (ER+) BC. Ki67 antigen was evaluated immunohistochemically in tumor specimens obtained before chemotherapy and at mastectomy. At post chemotherapy evaluation, tumor shrinkage greater than 50% was obtained in 60 patients (78.9%), 21 of them being complete responders (27.6%). As a whole, primary chemotherapy significantly decreased the number of Ki67 positive cells. More than 50% decrease in Ki67 expression was observed in 78.9% of patients attaining a clinical complete response (CR), in 44.7% of patients with partial remission (PR) and in 50.0% of non-responders, while an increase (>25%) in Ki67 expression was found in 5.3%, 18.4% and 18.7% of patients with CR, PR and non-response, respectively. Both CR and PR rates were superimposable in patients with ER+ and ER- primary BC, while the reduction in Ki67 expression was mainly found in ER+ cases. Patients with increased Ki67 expression from baseline, at the end of primary chemotherapy, had a shorter disease-free interval (70 months) with respect to patients with no change (88+ months) or decrease (87+ months), p<0. 05. To conclude, the activity of CMF + tamoxifen in primary BC does not seem superior to that expected administering CMF alone. The reduction in Ki67 expression, as a whole, correlated with clinical CR, but some individual discrepancies between tumor shrinkage and Ki67 pattern have been observed. The Ki67 reduction mainly confined to the ER+ primary BC suggests that tumor response in this subset may be linked to the reduction in proliferation activity, whereas other mechanisms such as apoptosis might be responsible for the tumor shrinkage in ER- tumors. Since the increase in proliferation activity after primary chemotherapy was associated with a greater recurrence rate and lower disease free interval, irrespective of tumor response, changes in proliferation activity after primary chemotherapy may represent a potentially available parameter that, in addition to the tumor response, can discriminate patients who would benefit from the cytotoxic treatment from patients who would not.

Clinicopathological features of early gastric cancer in younger versus older patients in a high incidence area of northern Italy.

AIMS: The relationship between the clinicopathological features of early gastric cancer and age were analysed in a retrospective study of 168 patients. METHODS: 168 patients, residents of the Region of Cremona, who had undergone surgery in the period 1978 to 1990 for early gastric cancer, were divided into two groups by age and compared. Group I (n = 89) consisted of patients less than 65 years of age and Group II (n = 79) of patients between 66 and 85 years of age. RESULTS: There were no significant differences between the two groups with respect to the sex ratio, tumour size, depth of tumour invasion, and 5-year survival rate. Group I patients showed more lymph node involvement (p < 0.01), cancer of the diffuse histological type (p < 0.01), and cancers located in the gastric body (p < 0.05). Conversely, Group II exhibited more cancers of the protruded (p < 0.05) and intestinal histological type (p < 0.01), and more adenomatous residue (p < 0.01). CONCLUSIONS: Our findings suggest that early gastric cancer may present differently in different age groups; persons 65 years of age and older are more likely to have early gastric cancer of the slow-growing type than middle-aged patients.

[Light-chain deposition disease. Presentation of a case]. / Malattia da depositi di catene leggere (lcdd). Presentazione di un caso.

A case of 66-years-old woman with mild renal failure due to deposition of K light chains on glomerular nodules, is reported. Monoclonal K light chains were found by immunofixation in serum and concentrated urine. Bone marrow examination showed a moderate increase of plasma cells, all stained for K light chains. Amyloid was not identified. No chemotherapy was started. Despite this, in the 15-months follow-up, renal function was preserved; no signs of myeloma, nor of extrarenal involvement were found. Careful follow-up is emphasized. The reason why light chains form amyloidoses or nodular deposits, like diabetic glomerulosclerosis of Kimmelstiel-Wilson, is briefly discussed, together with the differential diagnosis from other nephropathies.