Cutaneous and subcutaneous metastases of rectal cancer.

The occurrence of cutaneous metastatic disease from colorectal cancer is uncommon and typically signifies widespread disease with poor prognosis. Colorectal metastases usually occur within the first 3 years of follow up, and the median survival of patients after the appearance of cutaneous metastatic lesions is 18 to 20 months. We describe an unusual case of a 60-year-old woman with a metachronous skin lesion as the sole site of metastatic disease, and a relatively long interval between the appearance of skin metastases and death. The woman was found to have an adenocarcinoma of the rectum, a Dukes' C lesion, extending over the entire rectal wall into the perirectal fat; five of eight regional lymph nodes showed metastases. Adjuvant radiotherapy followed by chemotherapy was administered for about 1 year. A subcutaneous lump on the left abdominal wall found 16 months postoperatively was metastatic of rectal origin. A metastatic adenocarcinoma of rectal origin was found in a single left lower axillary node 26 months later. Despite metastatic work-up for the next 2 years, an enlarged and palpated metastatic left inguinal lymph node appeared and was subjected to radiation. Computerized tomography (CT) examination 5 years after the first presentation of the rectal tumor and almost 4 years after the diagnosis of abdominal skin metastases disclosed recurrent pelvic disease with severe left hydronephrosis. Treatment by systemic chemotherapy was partially successful, but she died 8 months after this chemotherapy was initiated.

Breast carcinoma: a report on the potential usage of the CC chemokine RANTES as a marker for a progressive disease.

BACKGROUND: High incidence and intensity of RANTES (CC chemokine) expression were noted in advanced breast carcinoma. OBJECTIVE: To present two cases of breast carcinoma patients in whom RANTES expression was analyzed in parallel to disease progression. RESULTS: Although no evidence of malignancy was detected in the axillary lymph nodes of the two patients, their disease progressed. The expression of RANTES in both patients was positive at diagnosis and predicted the clinical course. CONCLUSIONS: These results, combined with our previous findings on the correlation between RANTES expression and advanced breast carcinoma, suggest that the assessment of RANTES expression may be useful for the identification of patients with apparently poor prognosis who may benefit from aggressive treatment. The above results call for large-scale studies by numerous research groups to determine the prognostic value of RANTES expression.

CMF (cyclophosphamide, methotrexate, 5-fluorouracil) versus CNF (cyclophosphamide, mitoxantrone, 5-fluorouracil) as adjuvant chemotherapy for stage II lymph-node positive breast cancer: results by demographic and clinical subgroups.

A multicenter phase III randomized study comparing the efficacies of two adjuvant polychemotherapeutic regimens in 145 patients with stage II node-positive breast cancer: the standard chemotherapy combination, CMF (cyclophosphamide, methotrexate, 5-fluorouracil), and an experimental protocol, CNF (cyclophosphamide, mitoxantrone [Novantrone], 5-fluorouracil) in which mitoxantrone replaced methotrexate. The finding of a significant advantage ( p= 0.04) in the disease-free survival for those receiving mitoxantrone (mean survival 4.4 years for CNF versus 2.7 years for CMF) led the authors to break the data down in subpopulations to determine exactly which groups of women responded more favorably to CNF than CMF. An advantage in disease-free survival was found, most notable in four subgroups: Sephardic women, women less than 45 years of age, premenopausal women, and women with 4 to 10 positive axillary lymph nodes. Although the small numbers of women in each of these subgroups rule out drawing definitive conclusions, the trend merits further study to confirm these observations.

The CC chemokine RANTES in breast carcinoma progression: regulation of expression and potential mechanisms of promalignant activity.

Breast cancer progression may be affected by various cellular components expressed by the tumor cells and/or by microenvironmental factors. Many studies report the correlation between breast cancer progression and monocyte infiltration into the tumor site. We have identified recently the CC chemokine regulated on activation, normal T cell expressed and secreted (RANTES), a major monocyte chemoattractant expressed by breast tumor cells, as a potential contributor to breast cancer progression. In the present study, analysis of the regulation of RANTES expression demonstrates that the expression of RANTES in breast tumor cells is elevated significantly and in a synergistic manner by IFN-gamma and tumor necrosis factor-alpha. Identification of the mechanisms by which RANTES may contribute to breast cancer progression included the analysis of the potential ability of RANTES to act in paracrine and indirect mechanisms, as well as directly on the tumor cells, to promote disease progression. Our results suggest that breast tumor cell-derived RANTES may promote breast cancer progression by its partial contribution to monocyte migration into breast tumor sites. Moreover, RANTES promotes the expression of matrix metalloproteinase (MMP) 9 by THP-1 monocytic cells and elevates vascularity in chick chorioallantoic membrane assays. Tumor necrosis factor-alpha, a major monocyte-derived cytokine, was found to promote the expression of MMP9 and MMP2 by MCF-7 and T47D breast adenocarcinoma cells, respectively, and to induce the de novo expression of an additional proteolytic enzyme by T47D cells, presumably MMP9. The possibility that RANTES may act directly on breast tumor cells was supported by detection of the expression of the CCR5 RANTES receptor in biopsy sections of breast cancer patients and by the ability of RANTES to promote the expression of MMP9 by MCF-7 cells. In all, our study suggests that the expression of RANTES by breast tumor cells results not only in monocyte migration to the tumor site but also in protumorigenic activities of RANTES and of proinflammatory cytokines that may facilitate metastasis formation and contribute to disease progression.