Blood vessel invasion and axillary lymph node involvement as prognostic indicators for human breast cancer

Weigand, Ray A.; Isenberg, William M.; Russo, José; Brennan, Michael J.; Rich, Marvin A.

doi:10.1002/1097-0142(19820901)50:5<962::aid-cncr2820500526>3.0.co;2-x

Cited by 73 publications

(33 citation statements)

References 18 publications

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“…Unfortunately, our new histological assessment differs from the previous one, and argues against a relationship between PGs and tumour spread into vessels. Since pathologists vary in their histological assessment of tumour grade (Delides et al, 1982) and malignant cells in blood vessels (4.7-52%;Fisher et al, 1975;Borah et al, 1980;Weigand et al, 1982), this argument is not settled. Furthermore, perhaps a tumour total PG-LM production of at least 16 ng g-1 aids the dispersion of malignant cells, as judged by the absence of positive bone scans near to the time of surgery in patients whose primary tumours produced very low amounts of total PG-LM.…”

Section: Resultsmentioning

confidence: 99%

Breast cancer, prostaglandins and patient survival

Bennett

Stamford²,

Berstock³

et al. 1989

Br J Cancer

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Summary Prostaglandins may have both undesirable and desirable effects in malignant disease. Their possible roles in breast cancer were studied by examining the relationships between different variables and the amounts of prostaglandin-like material (PG-LM) extracted from 141 breast carcinomas. Univariate analysis indicates a direct correlation with patient age and menopausal status, with a greater yield from cancers of post-compared with pre-menopausal women. Tumours up to 2cm diameter yielded more PG-LM than those measuring >2-5cm. Although there was also a direct correlation with bone metastasis near to the time of surgery, this was because no positive bone scans occurred in patients whose tumours yielded little total PG-LM (<16ng PGE2 equivalents per g tissue). Since tumour PG-LM did not predict later spread to bone, and yields of > 16 ng g -' were similar in the positive and negative bone scan groups, tumour PG-LM appears to be unimportant for skeletal metastasis. There was no obvious relationship of tumour PG-LM to the grade of malignancy, tumour type, amounts of fibrous tissue (and therefore malignant cells), invasion of blood vessels and lymphatics or presence of plasma cells. Multivariate analysis indicates that disease-free survival is longest with an intermediate production of tumour total PG-LM. Of the 82 patients now dead, the cause was attributed to metastatic disease in 69 cases. No relationship of PG-LM to the length of survival was seen with univariate or multivariate analysis. However, when just the post-menopausal patients who died within the first 3 postoperative years were analysed, there was a highly significant inverse correlation between the tumour total PG-LM and the time to death. The reason(s) for these different findings on overall survival compared with just the patients who died are not understood, but the results may indicate that one or more other variables must co-exist with a high tumour PG-LM to hasten death.Many tumours can produce more prostaglandins (PGs) than the normal tissues in which they arise (Bennett, 1979(Bennett, , 1982(Bennett, , 1988. Similarly, more prostglandin-like material (PG-LM), assayed on rat gastric fundus which is most sensitive to PGE2, was extracted from homogenates of human mammary carcinomas than from benign tumours or macroscopically normal breast tissue (Bennet et al., 1977). Various PGs and related substances extracted from breast carcinomas were identified by Stamford et al. (1983) using gas chromatography-mass spectrometry; the products were arachidonate, 12-hydroxy-eicosatetraenoate (12-HETE), thromboxane B2, 15-keto-l 3,14-dihydro-TXB2, 6-keto-PGFJ,, 6,15-diketo-PGF1,,, 615-diketo-1 3,14-dihydro-PGF1,,, PGD2, PGE2 and PGF21,. Quantitative gas chromatography-mass spectrometry showed substantial amounts of 6-keto-PGF, . and some PGD2, PGE2 and PGF20,, with much higher yields of arachidonate (Stamford et al., 1986). It might be expected that these potent substances contribute to breast cancer, but the problem is complex because PGs have numerou...

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Section: Resultsmentioning

confidence: 99%

Breast cancer, prostaglandins and patient survival

Bennett

Stamford²,

Berstock³

et al. 1989

Br J Cancer

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“…Therefore, tumour cell emboli in lymph and blood vessels are considered to be the morphological correlates of BC metastasising to loco-regional lymph nodes (LNs) and distant haematogenous sites, respectively. The presence of lymphovascular invasion indeed has been correlated to the presence of LN metastases and to poor prognosis in patients with BC (Sampat et al, 1977;Nealon et al, 1979Nealon et al, , 1981Dawson et al, 1982Dawson et al, , 1986Weigand et al, 1982;Bettelheim et al, 1984;Berger et al, 1988;Rosen et al, 1989Rosen et al, , 1991Lee et al, 1990;Clayton, 1991;Clemente et al, 1992;Neville et al, 1992;Fisher et al, 1993a, b;Lauria et al, 1995). Recently, interest in (lympho)vascular invasion has been increased owing to addition of peritumoural (lympho)vascular invasion to the St Gallen criteria for selection of adjuvant systemic treatment in operable BC (Goldhirsch et al, 2005).…”

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confidence: 99%

“…One of the major challenges has been to distinguish intratumoural lymph and blood vessels on HE slides from retraction artefacts caused by tissue fixation and processing. Most authors only included vessels with a clear-cut endothelium (Sampat et al, 1977;Nealon et al, 1979Nealon et al, , 1981Dawson et al, 1982Dawson et al, , 1986Weigand et al, 1982;Bettelheim et al, 1984;Berger et al, 1988;Rosen et al, 1989Rosen et al, , 1991Orbo et al, 1990;Clayton, 1991;Clemente et al, 1992;Neville et al, 1992;Fisher et al, 1993a, b;Pinder et al, 1994;Lauria et al, 1995), missing small and collapsed intratumoural vessels or vessels completely filled with tumour cells. Therefore, some authors only studied peritumoural LVI and BVI (Clemente et al, 1992;Neville et al, 1992;Lauria et al, 1995) or used morphological and topographical criteria to identify LVI (Orbo et al, 1990).…”

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confidence: 99%

“…Therefore, some authors investigated 'vascular invasion', including both LVI and BVI (Berger et al, 1988;Pinder et al, 1994). Others tried to distinguish between both using blood vessel-specific characteristics such as typical blood vessel morphology or the presence of red blood cells or fibrin cloths (Weigand et al, 1982;Lauria et al, 1995). Lee et al (1986Lee et al ( , 1990) used morphologic and immunohistochemical criteria and more recently, blood vessels were identified based on FVIII-antigen immunohistochemical or van Gieson elastica stains (Kato et al, 2002(Kato et al, , 2003.…”

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confidence: 99%

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Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study

et al. 2006

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Recently, peritumoural (lympho)vascular invasion, assessed on haematoxylin -eosin (HE)-stained slides, was added to the St Gallen criteria for adjuvant treatment of patients with operable breast cancer (BC). New lymphatic endothelium-specific markers, such as D2-40, make it possible to distinguish between blood (BVI) and lymph vessel invasion (LVI). The aim of this prospective study was to quantify and compare BVI and LVI in a consecutive series of patients with BC. Three consecutive sections of all formalin-fixed paraffinembedded tissue blocks of 95 BC resection specimens were (immuno)histochemically stained in a fixed order: HE, anti-CD34 (panendothelium) and anti-D2-40 (lymphatic endothelium) antibodies. All vessels with vascular invasion were marked and relocated on the corresponding slides. Vascular invasion was assigned LVI (CD34" or~/D2-40") or BVI (CD34"/D2-40~) and intra-(contact with tumour cells or desmoplastic stroma) or peritumoural. The number of vessels with LVI and BVI as well as the number of tumour cells per embolus were counted. Results were correlated with clinico-pathological variables. Sixty-six (69.5%) and 36 (37.9%) patients had, respectively, LVI and BVI. The presence of 'vascular' invasion was missed on HE in 20% (peritumourally) and 65% (intratumourally) of cases. Although LVI and BVI were associated intratumourally (P ¼ 0.02), only peritumoural LVI, and not BVI, was associated with the presence of lymph node (LN) metastases (p peri ¼ 0.002). In multivariate analysis, peritumoural LVI was the only independent determinant of LN metastases. Furthermore, the number of vessels with LVI was larger than the number of vessels with BVI (P ¼ 0.001) and lymphatic emboli were larger than blood vessel emboli (P ¼ 0.004). We demonstrate that it is possible to distinguish between BVI and LVI in BC specimens using specific lymphatic endothelium markers. This is important to study the contribution of both processes to BC metastasis. Furthermore, immunohistochemical detection of lymphovascular invasion might be of value in clinical practice.

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“…It has been more difficult to identify invasion of small vessels and capillaries and in the larger vessels surrounded by elastic tissue in breast cancer in routine haematoxylin and eosin (H&E)-stained tissue sections than in gastric or colorectal cancer. A wide range of frequencies has been reported for BVI among patients with breast cancer and the prognostic significance of BVI has not yet been made clear (Weigand et al, 1982;van de Velde et al, 1986;Gasparini et al, 1994;Lauria et al, 1996;Kato et al, 2000Kato et al, , 2002.…”

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confidence: 99%

The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer

et al. 2003

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This study was undertaken to examine the interaction between the combination of angiogenesis and blood vessel invasion (BVI) and haematogenous metastasis, and to determine the prognostic significance of that combination in predicting 20-year relapse-free survival (RFS) and overall survival (OS) rates in primary breast cancer. Five hundred and nine patients were studied. We investigated 11 factors, including average microvessel count (AMC)/BVI, lymph-node status (n), clinical tumour size (T), histological grade (HG), lymphatic vessel invasion (LVI), p53, proliferating cell nuclear antigen (PCNA), c-erbB-2, mitotic index (MI), apoptotic index, and tumour necrosis (TN). Blood vessel invasion was detected by both factor VIII-related antigen and elastica van Gieson staining. To evaluate the best objective method to quantify microvessel density in angiogenesis, AMC was employed. The rate of AMC-high and BVI-positive tumours was 32.6 and 29.3%, respectively. That of both AMC-high and BVI-positive tumours was 10.1%. Univariate analysis showed that AMC/BVI, n, T, HG, LVI, p53, PCNA, MI, and TN were significantly predictive of RFS and OS. By multivariate analysis, AMC/BVI was the strongest independent prognostic factor for 20-year RFS (relative risk (RR) ¼ 5.5; Po0.0001) and for 20-year OS (RR ¼ 4.3; Po0.0001). Lymph-node status was still considered a powerful prognostic indicator; however, the combination of AMC and BVI provided more reliable prognostic information than lymph-node status for haematogenous dissemination.

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Blood vessel invasion and axillary lymph node involvement as prognostic indicators for human breast cancer

Cited by 73 publications

References 18 publications

Breast cancer, prostaglandins and patient survival

Breast cancer, prostaglandins and patient survival

Distinguishing blood and lymph vessel invasion in breast cancer: a prospective immunohistochemical study

The combination of angiogenesis and blood vessel invasion as a prognostic indicator in primary breast cancer

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