Quantification of stromal reaction in breast carcinoma and its correlation with tumor grade and free progression survival.

Cancer progression results from a complex interplay between tumor cells and the extracellular milieu. In breast carcinoma, the stromal microenvironment has been suggested to play a major role in promoting tumor growth, progression, and invasion. The stroma of 154 resected specimens of invasive breast carcinoma of no special type was quantified using a digital image analyzer. Statistical analyses were performed between the quantity of stroma and survival, as well as between progression-free survival and clinicopathological data. Levels of myofibroblastic stroma varied from 0-46%, with a median of 15.1% and a standard deviation of 7.5. The myofibroblastic stromal reaction was statistically greater in grade 2 and 3 tumors (p = 0.029). Furthermore, there was a trend for worse progression-free survival in the group of node-negative tumors with strong smooth-muscle actin stromal expression (Log rank = 0.075). The present study demonstrates that the myofibroblastic reaction of breast invasive carcinoma of no special type is not merely a passive reaction, but seems to be an integral part of the neoplastic process by facilitating tumor progression and invasion. Additional, larger studies on mechanisms of stromal change are needed and may potentially lead to novel treatments.

Automatic measurement of epithelium differentiation and classification of cervical intraneoplasia by computerized image analysis.

BACKGROUND: The feasibility of evaluating an objective grading of cervical intraneoplasia lesions (CIN) is attempted using an automatic computerized system able to measure several valuable parameters with special reference to epithelium differentiation. METHODS: 4 groups of 10 images each were selected at random from 68 consensus images coming from 80 archival cervical biopsies, normal (n = 10), CIN 1 (n = 10), CIN 2 (n = 10), CIN 3 (n = 10). Representative images of lesions were captured from the microscopic slides and were analyzed using mathematical morphology, with special reference toVoronoï tessellation and Delaunay triangulation. Epithelium surface, nuclear and cytoplasm area, triangle edge and area, total and upper nuclear index were precisely measured in each lesion, and discriminant coefficients were calculated therewith. A dilation/erosion coefficient was automatically defined using triangle edge length and nuclear radius in order to measure the epithelium ratio of differentiation. A histogram ratio was also automatically established between total nuclei and upper nuclei on top of differentiated epithelium. With the latter two ratios added to the nucleo-cytoplasmic ratio, a cervical score able to classify CIN is proposed. RESULTS: There is a quasi-linear increase of mean cervical score values between normal epithelium and CIN 3: (27) for normal epithelium, (51) for CIN 1, (78) for CIN 2 and (100) for CIN 3, with significant differences (P < 0.05). CONCLUSION: Our results highlight the possibility of applying a cervical score for the automatic grading of CIN lesions and thereby assisting the pathologist for improvement of grading. The automatic measure of epithelium differentiation ratio appears to be a new interesting parameter in computerized image analysis of cervical lesions.

Microvessel and lymphatic density in tubular carcinoma of the breast: comparative study with invasive low-grade ductal carcinoma.

Tubular carcinoma (TC) of the breast is an uncommon variant of ductal carcinoma, which has an extremely low metastatic potential and an excellent prognosis. Studies concerning the vascular and lymph vessel status in TC are not numerous and hampered by a lack of specific markers. We immunohistochemically analysed the expression of CD31 and D2-40 antibodies in 15 TC measuring less than 2cm in diameter. We compared the results with those observed in 30 low-grade ductal breast carcinomas (LGDC) of no specific type with similar dimensions. Neither microvascular density (MVD) nor lymphatic vessel density (LVD) was statistically different in the groups: MVD was 26.5+/-28.2 and 32.1+/-17.9 vessels/mm(2) in TC and LGDC, respectively (P=0.08). LVD, low in both tumour types, was 0.5+/-0.3 and 0.6+/-0.4 vessels/mm(2), respectively (P>0.1). These data suggest that the favourable prognosis and the low rate of lymph node metastases in TC are not explained by lymphangiogenetic and angiogenetic potential and are supported by recent analyses in the literature.

Endometrial vascularization in levonorgestrel intrauterine device users; computerized microvessel measurement study.

Levonorgestrel use in the levonorgestrel intrauterine device (LNG-IUS) induces vascular distension within the superficial layer of the endometrium and massive pseudodecidualization. With a computer-assisted image analysis system, we objectively measured the vascular bed in LNG-IUS users and compared it to the physiological endometrium. A study was undertaken on 25 women using LNG-IUS, in an outpatient procedure at the time of removal of the IUS and compared with 11 normally cycling women (control group). Suction curette specimens were obtained just after retrieval of the IUS, and immunohistochemistry was carried out with a specific marker of the endothelial cells (CD31). Number of vessels decreased in the LNG-IUS group to 60/mm2 versus 124/mm2 in the control group, and mean vessel area increased to 1255 microm2 versus 157 microm2, respectively, in the control group. The decrease in mean vascular density and the increase of mean vessel area in the LNG-IUS group, compared to the control group, were both highly significant (p<.001).