Terttu Toivonen

Tenascin-C expression in invasion border of early breast cancer: a predictor of local and distant recurrence.

We have recently demonstrated an association between distant metastasis and the expression of the extracellular matrix glycoprotein tenascin-C (Tn-C) in the invasion border of small axillary node-negative breast carcinomas. Our purpose was to assess the relationship between the expression of Tn-C in the tumour invasion border and several histopathological and biological variables and to compare their usefulness in predicting local and distant disease recurrences. The original patient group consisted of 143 women with axillary node-negative breast cancer (one bilateral) treated with breast-conserving surgery and post-operative radiotherapy, and followed for a median of 8 years. Because of the small number of recurrences an additional group of 15 similarly treated women with recurrent breast cancer was also studied. The size of the tumour, its histology, including a possible intraductal component, and grade were re-evaluated. The expression of erbB-2, p53, Ki-67 and Tn-C was evaluated by immunohistochemistry. Ploidy and S-phase fraction (SPF) were assessed by flow cytometry. The only statistically significant prognostic factor for local recurrence was Tn-C expression in the invasion border. For metastasis Ki-67 positivity, tumour size and Tn-C expression in the invasion border were statistically significant, but Ki-67 positivity was the only independent prognostic factor. Tn-C expression in the invasion border was associated with a higher proliferation rate measured by Ki-67 and SPF, which is consistent with the suggested growth-promoting activity of Tn-C. Tn-C may be a useful marker in selecting patients for adjuvant therapies to reduce the rate of both local and distant cancer recurrences.

Expression of Tenascin-C in intraductal carcinoma of human breast: relationship to invasion

Tenascin-C (Tn-C) is an extracellular matrix glycoprotein that appears in areas of epithelial-mesenchymal interaction during fetal development and in neoplasia. The immunohistochemical expression of Tn-C and its relationship to histology, nuclear grade, microinvasion, oestrogen (ER) and progesterone receptors (PR), and to cell proliferation measured by Ki-67 expression were studied in 89 intraductal breast carcinomas (DCIS). Periductal Tn-C was noted in 87% and stromal Tn-C in 25% of the tumours. Stromal expression was associated with moderate to strong periductal expression and microinvasion. Periductal expression was associated with comedo-type, nuclear grade, microinvasion, Ki-67 expression, and lack of PR. The distribution of Tn-C was compared in DCIS and in the intraductal component from another series of small axillary node-negative invasive breast carcinomas (n = 44). Tn-C was present in the stroma of pure DCIS in 25% and in the intraductal component of the other series in 82%. Thus, stromal or moderate to strong periductal Tn-C expression in DCIS may relate to early invasion. DCIS with weak periductal or missing Tn-C expression may be a subgroup with benign behaviour.

Expression of tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis

Tenascin (Tn) is an extracellular matrix glycoprotein transiently expressed in epithelial‐mesenchymal interaction areas during embryogenesis. Tn is expressed in a limited manner in adult tissues but emerges during wound healing and tumorigenesis. We have studied Tn expression by immunohistochemistry in 137 small node‐negative breast cancers treated with breast‐conserving surgery and post‐operative radiotherapy during 1985–1996. None of the patients had undergone any adjuvant hormonal therapy or chemotherapy. Stromal Tn expression itself could not predict distant metastasis. However, Tn staining in the area of the invasion border seemed to be a strong predictor of distant metastasis, with an estimated 5‐year metastasis‐free survival (MFS) of 85% in Tn‐positive cases compared to 98% in Tn‐negative ones. The prognostic impact of Tn in the invasion border on MFS was stronger than that of tumour size and grade. This staining appears to be a useful adjunct for the estimation of breast‐cancer metastasis.

The clinical value of parasternal sentinel node biopsy in breast cancer

BackgroundLymphoscintigraphy (LS) with sentinel node (SN) biopsy is proposed to provide a feasible method to complete lymphatic staging in breast cancer. The aim of this study was to evaluate the clinical value of parasternal SN biopsy.MethodsA total of 984 consecutive patients with clinical stage T1/2N0 invasive breast cancer who underwent LS and SN biopsy were included in the study. A prospectively collected database was used. An intratumoral injection of 50 to 145 MBq of 99mTc-labeled human albumin colloid (Nanocoll) was used for preoperative LS.ResultsLS showed the axillary SN in 844 (86%) cases and the parasternal SN in 138 (14%) cases. The median number of visualized parasternal SN was 2 (range, 1–6). Visualization of the parasternal SN was more common in patients with mediocentral tumors (81 of 399; 20%) and in patients with lateral tumors (56 of 585; 10%; P < .0001). Parasternal SNs were visualized more often, in 100 (17%) of 584 patients without axillary metastases compared with 38 (10%) of 400 patients with metastatic axillary nodes (P = .0006). Parasternal SNs were harvested successfully in 121 (88%) patients with visualization of those nodes. Parasternal SN metastases were detected in 18 patients, with a median of 1 metastasis (range, 1–4 metastases). Eight of these 18 patients were axillary node negative.ConclusionsParasternal SN biopsy results in upstaging in 2% of all breast cancer patients who undergo SN biopsy. The clinical value of the procedure seems insignificant, although it may influence the adjuvant treatment regimen in some patients.

Cathepsin-D, urokinase plasminogen activator and type-1 plasminogen activator inhibitor in early breast cancer : An immunohistochemical study of prognostic value and relations to tenascin-C and other factors

Cytosolic determinations of cathepsin-D (cath-D), urokinase plasminogen activator (uPA) and its specific inhibitor PAI-1 have shown an association with adverse prognosis in breast cancer. Our aim was to study the distribution of these markers in small axillary node-negative breast carcinomas using immunohistochemistry and relate the semiquantitative results to known prognostic factors, the expression of tenascin-C (Tn-C) in invasion border of the tumour and prognosis. All the 158 women (159 tumours) were treated with breast conserving surgery and postoperative radiotherapy. Cytoplasmic immunoreactivity for cath-D was seen in carcinoma cells in 47% and in stromal cells in 44%. Nearly all tumours expressed uPA and PAI-1, which were categorized to cytoplasmic expression in carcinoma cells and diffuse stromal expression and quantified – / + / ++ / +++ and further dichotomized for purposes of analysis. Expression of uPA and PAI-1 in stromal fibroblasts was recorded as – / +. Cytoplasmic and stromal cell cath-D contents were associated with grade, proliferation, Tn-C expression in the tumour invasion border and the development of distant metastasis. In multivariate analysis stromal cath-D proved to be an independent prognostic factor for metastasis. Stromal expression of uPA was associated with an increased risk of local recurrence; otherwise high levels of uPA did not associate with other prognostic factors nor with prognosis. Fibroblastic expression of PAI-1 showed an association with both local and distant disease recurrence. However, no consistent association between the immunohistochemically quantified uPA and PAI-1 and prognosis was found. In conclusion, immunohistochemical determination of cath-D seems to be a viable method to predict a higher risk of metastasis but not local recurrence in small axillary node-negative breast carcinomas.

A randomised public-health trial on automation-assisted screening for cervical cancer in Finland : Performance with 470,000 invitations

Our objective was to evaluate automation‐assisted screening, in comparison to the conventional method, in a routine population‐based cervical cancer‐screening programme. Our study is based on an individually randomised design involving approximately 160,000 invitees and 110,000 attendees every year. From 1999 to 2001, 471,297 women were invited to attend and 330,445 smears were screened (attendance rate 70.1%), of which 220,254 were tested conventionally and 110,191 were tested using the automation‐assisted method. Cytologic Papanicolaou group II findings were reported slightly more often (RR = 1.04) in the automation‐assisted method than in the conventional screening arm. There were 1,291 cases of histologically confirmed dysplasia or carcinoma (0.4% of the screened), one‐third of which were severe dysplasia or a more severe finding (CIN3+). The detection rates of histologically verified findings were similar between the 2 screening arms. In Finland, the screening programme has been effective. As the detection rates, particularly of CIN3+, were similar between the screening arms, we will continue the automation‐assisted method in the routine screening programme. Further follow‐up for interval cancer incidence is required, however, to measure if the effect of screening is the same between the arms. A similar evaluation design is feasible to any other major or competing modification of the screening test or other element in the programme.

Randomized evaluation trial on automation-assisted screening for cervical cancer: Results after 777,000 invitations

Objectives: New cervical screening methods have been developed. They seem to become accepted in routine use without randomized trials, within existing screening programmes. Our aim was to evaluate, in a randomized setting, the performance of automation-assisted cytological screening in routine use compared with conventional Papanicoalou (Pap) screening. Setting: This prospective study was based on a 1:2 individually randomized design. Altogether 777,144 women were invited to attend the routine screening programme. Results: Automation-assisted screening found more Pap class III (LSIL+) findings compared with conventional study arm, relative risk (RR) 1.08 (confidence interval 1.01–1.15). Also, detection rates of verified pre-cancers were more common in automation-assisted arm, RR 1.11 (1.02–1.21). Conclusions: Automation-assisted screening performed well compared with conventional screening. The difference was smaller than reported in non-randomized studies. A new technique may assume several years to reach the ultimate quality and can add costs without improving efficacy. Follow-up of prevented cervical cancers is required.