Serum and tissue CTACK/CCL27 chemokine levels in early mycosis fungoides may be correlated with disease-free survival following treatment with interferon alfa and psoralen plus ultraviolet A therapy.

BACKGROUND: Neoplastic T-cell recruitment into the skin is a critical step in the pathogenesis of mycosis fungoides (MF), and the cutaneous T-cell attracting chemokine, CTACK/CCL27, might be involved. OBJECTIVES: To investigate the clinical and prognostic significance of CTACK/CCL27 levels in patients with early-stage MF. METHODS: Serum samples and skin biopsy specimens were collected from 15 patients at the time of diagnosis and after the end of treatment with psoralen plus ultraviolet A/interferon alfa-2b combination therapy. Serum samples were also collected from 20 healthy donors as controls. CTACK/CCL27 serum levels were analysed by enzyme-linked immunosorbent assays. CTACK/CCL27 tissue expression was determined by immunohistochemistry on skin biopsy specimens taken at diagnosis and after therapy. Event-free survival was taken as the primary clinical outcome. RESULTS: In patients with MF at diagnosis, CTACK/CCL27 serum levels were not significantly different from healthy controls, whereas CTACK/CCL27 expression in the skin was increased in 87% of cases compared with normal controls. After therapy, all patients obtained a clinical complete remission, serum levels did not change significantly and tissue expression remained abnormal in 80% of patients, even if complete histological remission was recorded. Serum levels were not significantly different in cases with different intensity of cutaneous immunostaining. Eight patients experienced a relapse: the combination of high CTACK/CCL27 levels both in sera and skin increased the probability of experiencing an event at 51 months from 36% to 83%. CONCLUSIONS: Our data seem to indicate that CTACK/CCL27 levels in skin and sera after therapy might be correlated with risk of recurrence.

Ras p21 immunostaining in early stage squamous cervical carcinoma: relationship with lymph nodal involvement and 72 kDa-metalloproteinase index.

BACKGROUND: Ras p21 expression seems to be associated with aggressiveness of neoplastic growth and metastatic potentially in human solid tumors. In our series of early-stage squamous cervical carcinoma, we evaluated ras p21 expression with respect to lymph nodal involvement; the aim was to analyse the ras p21 immunostaining as potential marker of lymphatic spread, and investigate the relationship between ras p21 expression and 72 kDa-metalloproteinase immunostaining. PATIENTS AND METHODS: 46 patients with FIGO stage I squamous cell cervical carcinoma, who had undergone primary radical surgery with systematic pelvic and paraaortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, were recruited from our series of 59 consecutive cases, and included the study. Any characteristic that could be relevant for prognosis was recorded such as: histologic grade of differentiation, tumor size, lymphatic spread, or adjuvant radiotherapy. Immunohistochemical staining was performed using the avidin-biotin peroxidase complex method (LSAB, Dako, Copenhagen, Denmark). Monoclonal antibody anti-pan ras (Ab-1) (Oncogene Science) and affinity purified rabbit anti-72 kDa-metalloproteinase antibody were used. Positivity for ras p21 was evaluated by semiquantitative analysis, while 72 kDa-metalloproteinase staining was expressed as the percentage of positive cells per 10(3) counted neoplastic cells (index). RESULTS: The expression of ras p21 was observed in 31 patients (67%) with FIGO stage I squamous cervical carcinoma. No connection was found between ras p21 expression and tumor size (P = 0.2), or histologic grade (P = 0.9), while a significant relationship was observed with respect to lymph nodal status (p = 0.048). By analysing 72 kDa-metalloproteinase immunostaining, ras p21 positive carcinomas showed significantly higher 72 kDa-metalloproteinase index than the negative ones (mean + standard deviation, 23.3% + 7.7% and 13.8% + 5.1% respectively, and P < 0.001). CONCLUSIONS: Though the relatively small size of our series does not allow any definitive conclusion, a significant relationship between ras p21 expression and risk of lymphatic spread was detected in early-stage cervical carcinoma. ras p21 positivity seems to be an indicator of neoplastic aggressiveness and lymphatic spread, and is associated with significantly higher expression of 72 kDa-metalloproteinase.

The 72-kDa metalloproteinase immunostaining in cervical carcinoma: relationship with lymph nodal involvement.

OBJECTIVE: In the present study we detected 72-kDa metalloproteinase expression in our series of early stage cervical carcinomas and analyzed the relationship between 72-kDa metalloproteinase staining and risk of nodal involvement with the goal of identifying a parameter useful in predicting the metastatic potential of lesions. MATERIALS AND METHODS: The medical records of 34 patients with FIGO stage I squamous cell cervical carcinoma who had undergone primary radical surgery with systematic pelvic and para-aortic lymphadenectomy (Piver's type III) at the Institute of Gynecologic and Obstetrics, Ancona University, between January 1988 and January 1993 were recruited from our series of 57 consecutive cases and reviewed. Any characteristic that could be relevant for prognosis was recorded in all of the cases: histologic grade of differentiation, tumor size, lymphatic spread, and adjuvant radiotherapy. Immunohistochemical staining was performed on serial sections of tumors using the avidin-biotin complex technique (Vector Laboratories, Burlingame, CA). The affinity-purified rabbit anti-72-kDa metalloproteinase antibody was used. Positive staining was expressed as a percentage of positive cells per 10(3) counted neoplastic cells (the 72-kDa metalloproteinase index). RESULTS: The tissue 72-kDa metalloproteinase immunoreactivity was diffusely expressed in all cervical carcinomas (ranging from 8.6 to 51.9%, with a median of 17.8%) and showed a significant relationship with respect to lymphatic spread. In the presence of lymph nodal involvement, the 72-kDa metalloproteinase index was significantly higher than in the absence of nodal metastasis (32.9 +/- 12.2% versus 18.1 +/- 9.0%, means +/- standard deviations with P = 0.001); a significant relationship was also observed between the 72-kDa metalloproteinase index and the number of positive nodes (r = 0.8, with P = 0.01). No significant relationship was defined with respect to the other prognostic parameters. The Cox proportional hazard analysis showed a significant relationship between the 72-kDa metalloproteinase index and disease-free survival (P < 0.0001) that was independent of tumor size, nodal involvement, and lymphvascular space invasion. CONCLUSIONS: Although the small numbers do not allow any definitive conclusion, a significant relationship between the 72-kDa metalloproteinase index and the risk of lymphatic spread is defined in early stage cervical carcinoma. The 72-kDa metalloproteinase immunostaining seems to have a prognostic value, suggesting the possibility of an association between neoplastic aggressiveness and 72-kDa metalloproteinase expression.