Role of lymphagenesis in neovascularisation

Role of lymphagenesis in neovascularisation SiR-Ellis and Fidler (Aug 12, p 388) underscore a critical role for neovascular suppressive agents in the treatment of breast cancer. However, it is important not to limit analyses to the blood vascular system and to understand the part played by the lymphatic vascular system, particularly in breast cancer. Although the lymphatic role in metastasis has been noted,’ lymphagenesis (lymphatic vessel formation) is generally overshadowed by the greater emphasis placed on the blood vascular system. Lymphatic vessels are seen in breast carcinomas, including areas of ductal carcinoma in situ (figure), and their development may be analogous to the process that occurs at sites of infectionIn 1907, Ryall’ referred to malignant growth and metastasis as "cancer infection", because of the resemblance of this process to pathogenic infections. In light of the current understanding of lymphagenesis, his comparisons seem more appropriate than ever. In wounding, lymphagenesis facilitates the drainage and filtration of infectious agents to prevent dissemination into the bloodstream. If this system is impaired, noxious agents may enter the bloodstream-so too may malignant cells. In fact, it has been suggested that the lymphatics are the main channels for tumour-cell dispersion, because of the lack of a basement membrane’ and their permeability.’ In this respect, it is not surprising that the number of lymphatic vessels, rather than the number of blood vessels, has the greater prognostic significance for recurrent disease.1.5 Ducts of the normal breast are associated with an elaborate system of lymphatic channels’ that accommodate the unique requirements for milk production by this organ. This network supports the lymphatic oedema and

subsequent drainage that is a menstrual cycle. Lymphatic

recurrent process of the associations with ductal carcinoma can support the diffusion from the bloodstream of oxygen, nutrients, and other lymph components to sustain tumour growth. In turn, this well-established system for fluid transport provides a potential avenue for early metastasis. A greater understanding of the mechanisms that regulate lymphagenesis and angiogenesis in tumours is required. Continued advances in this field will reveal the complementary parts played by both systems in the progression and metastasis of cancer.

Johannes P van Netten, Teara L Ashby, Michael J Ashwood-Smith, Nicholas G van der Westhuizen Immunoassay and Special Development Laboratory, Royal Jubilee Hospital, Victoria,

*Stephen A Cann,

British Columbia, Canada V8R 1J8

Maehara Y, Oshiro T, Baba H, Ohno S, Kohnoe S, Sugimachi K. Lymphatic invasion and potential for tumor growth and metastasis in patients with gastric cancer. Surgery 1995; 117: 380-85. Casey-Smith JR. The lymphatic system in inflammation. In: The inflammatory process, 2nd ed. New York, NY: Academic Press, 1973: 161-204. Ryall C. Cancer infection and cancer recurrence: a danger to avoid in operations. Lancet 1907; ii: 1311-16. Hartveit F. Attenuated cells in breast stroma: the missing lymphatic system of the breast. Histopathology 1990; 16: 533-43. Horak ER, Harris AL, Stuart N, Bicknell R. Angiogenesis in breast cancer: regulation, prognostic aspects, and implications for novel treatment strategies. Ann N Y Acad Sci 1993; 698: 71-84.

1

2

3 4 5

Pathologist

or

laboratory physician?

SrR-I agree wholeheartedly with Joshi’s comments (July 22, 258) about misunderstanding among clinical colleagues of the role of pathologists in clinical laboratories, of which we have all had some experience. A pathologist with a medical degree is a clinician, and by having a higher qualification in any pathology discipline will only reinforce his status as a clinician. A laboratory-based physician is, therefore, in a unique position to link the patient’s clinical details with laboratory evidence, and to give advice regarding diagnosis and treatment of many diseases. It is also worth emphasising that laboratory tests, as indeed does any other diagnostic service, confer a scientific flavour to clinical cases, without which they would be boring and bland. p

M A Al-Jubouri Department of Clinical Biochemistry,

Rotherham General

Hospital, Rotherham,

South Yorkshire S60 2UD, UK

Figure: Infiltrating ductal carcinoma vascularisation Top: formalin-fixed

of the breast

showing

section stained with von Willebrand factor monoclonal A 082 (Dakopatts, Glostrup, Denmark) reveals crosssectional staining of blood vessels. Bottom: frozen section stained with MU170-UC monoclonal antibody (BioGenex, San Ramon, CA) shows lymphatic endothelia in predominantly longitudinal sections, reflecting their unique morphology. Bar=200 m.

SiR-I agree with Joshi’s view about the professional activities of pathologists, and I feel the same discouragement he describes when "everybody including clinician colleagues, friends, and strangers whom you meet for the first time regards you as a dead person’s doctor". Despite elegant semantic discussions, the situation Joshi describes is realistic. Pathologists should be aware of the boundaries of the specialty: this means not only the physical limits-ie, the laboratory or the post-mortem room-but also the scenario in which they develop their professional work. They need not only to know their own field thoroughly, but also to have a wide knowledge of clinical medicine and surgery. They have to be able to tell clinicians whether a lesion is benign or malignant, as well as the surgeon the extent of disease, the adequacy of the excision, and other pertinent information about surgical specimens. They should also be able to comment on whether additional therapy may be necessary and give information on the prognosis of the disease.’1 Clinicians should be fully aware of the potential and limitations of the specialty. They should know that a microscopic diagnosis is a subjective evaluation that only 903