Invasive micropapillary carcinoma of the breast with minimal regional lymph node metastasis regardless of the huge size: report of a case.

We present a 38-year-old premenopausal Japanese woman with invasive micropapillary carcinoma (IMC) of the left breast with minimal lymph node metastasis despite a huge size. The patient noticed a left breast mass and a bloody nipple discharge 2 years before admission. On admission, physical examination revealed a huge, elastic hard mass with skin ulcer 12x12 cm in diameter occupying the entire left breast. The patient underwent modified radical mastectomy with level III lymph node dissection, and the defect was reconstructed with a vertical rectus abdominis myocutaneous flap. Histopathologically, IMC comprised about 60% of the tumor, admixed with papillotubular and mucinous carcinoma. Only one of twenty-five lymph nodes had tumor metastasis. The patient remains well 8 months postoperatively without any signs of recurrence.

Unproductive cleavage and the inactivation of protease-activated receptor-1 by trypsin in vascular endothelial cells.

1 Using fura-2 fluorometry of [Ca(2+)](i) in response to thrombin, trypsin and protease-activated receptor activating peptides (PAR-APs), we determined whether trypsin cleaves protease-activated receptor 1 (PAR1) and activates it in the endothelial cells of the porcine aortic valves and human umbilical vein. 2 Once stimulated with thrombin, the subsequent application of trypsin induced a [Ca(2+)](i) elevation similar to that obtained without the preceding stimulation with thrombin in the valvular endothelial cells. However, the preceding stimulation with trypsin abolished the subsequent response to thrombin, but not to bradykinin or substance P. 3 The response to PAR1-AP (SFLLRNP) was significantly (P<0.05) reduced by the preceding stimulation with thrombin and PAR1-AP in the valvular endothelial cells, while, importantly, it remained unaffected by the preceding stimulation with either trypsin or PAR2-AP (SLIGRL). The response to PAR2-AP was reduced by the preceding stimulation with trypsin and PAP2-AP. PAR1-AP attenuated the subsequent responses not only to thrombin and PAR1-AP but also to trypsin and PAR2-AP, while PAR2-AP specifically attenuated the subsequent responses to trypsin and PAR2-AP. 4 In human umbilical vein endothelial cells, a higher affinity PAR1-AP (haPAR1-AP) (Ala-pF-Arg-Cha-HArg-Tyr-NH(2)) specifically attenuated the responses to thrombin but not trypsin. On the other hand, the response to haPAR1-AP was significantly (P<0.05) attenuated by the preceding stimulation with thrombin but not trypsin. 5 In conclusion, trypsin cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the trypsin-cleaved PAR1 was no longer responsive to thrombin.