Prognostic impact of mitotic index of proliferating cell populations in cervical cancer patients treated with carbon ion beam

BACKGROUND:

The authors previously reported that the mitotic index of a proliferating cell population (pMI) was a potent prognostic factor in cervical cancer patients treated with photon beam therapy. In this study, they investigated whether the pMI accurately predicted prognosis in cervical cancer patients treated with carbon ion beam.

METHODS:

Tissue sections were obtained from 27 consecutively treated patients with stage IIIB bulky (19 patients) and stage IVA (8 patients) squamous cell carcinomas of the cervix treated with carbon ion beam at the National Institute of Radiological Sciences, Japan, as a phase I/II study with dose escalation methodology (52.8‐72 grays equivalent radiation dose/24 fractions). The mitotic index (MI) and Ki‐67 labeling index (Ki‐67‐LI) were determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. The pMI was calculated using the following formula: pMI = MI/Ki‐67‐LI.

RESULTS:

The pMI ranged from 0.6 to 8.9 (mean, 3.9 ± 2.6; median, 3.2). Twelve of the 27 specimens had a pMI >3.5. The local control rate in tumors with a pMI >3.5 was 17%, significantly lower than the 73% in the tumors with a pMI <3.5 (P = .005). Multivariate analysis indicated that the pMI had the strongest impact on local control (standard regression coefficient = 0.48, P = .002) among the variables, including clinical stage, irradiated dose, age, and tumor volume.

CONCLUSIONS:

These results suggest that a high pMI is an indication of a poorer prognosis, and is a powerful prognostic factor in patients with squamous cell carcinomas of the cervix treated with carbon ion beam therapy. Cancer 2009. © 2009 American Cancer Society.     

Angiosarcoma of the breast: Report of a case and its findings of MRI

A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema. Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on T1-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on T1-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence. This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.     

A case of intracranial arteriovenous fistula in an infant with neurofibromatosis type 1

INTRODUCTION: Reported cases of arteriovenous fistula (AVF) with neurofibromatosis type1 (NF1) are rare. CASE REPORT: In this paper we report the first case of intracranial AVF in an NF1 infant who developed heart failure. Endovascular treatment using coils successfully obliterated the AVF. The mechanism underlying the AVF in this case was believed to be a congenital mesenchymal abnormality of the intracranial vessels. DISCUSSION: The mechanism underlying the development of heart failure in this case is also discussed.     

Morphological and biochemical evidence that scrapie-associated fibrils are derived from aggregated amyloid-like filaments.

The membrane fraction from scrapie infected mouse brains was dissolved in saturated urea, centrifuged on a 10 to 50% glycerol gradient at 35,000 rpm for 24 h, and fractionated from the bottom of the tube into 11 fractions. PrP was detected throughout the gradient. However, the relative PrP concentrations of fractions 4 and 8 were the highest. The relative PrP concentration versus protein concentration of fractions 1 to 4 was higher than that of the other fractions. Scrapie infectivity also was detected in all fractions. Fractions 2, 3, 4, 7, and 8 produced the shortest incubation periods. Positively stained filamentous aggregates with sizes varying from about 40 x 60 nm to more than 4 microns were observed in fractions 2 and 4 by negative staining. These resembled amyloid filaments. Congo red-stained aggregates showed birefringence under polarized light. Aggregation of the filamentous aggregates was observed by incubation with anti-mouse SAF serum. Fine fibrils 10-18 nm in width were partially dissociated from the aggregates by brief exposure to the detergent Sarkosyl. These facts suggest that SAF are not products of self-assembly from subunit structures liberated from membranes by exposure to detergent, but exist as aggregates of amyloid-like filaments from which SAF are dissociated by detergent extraction.     

Lysosomal generation of amyloid β protein species in transgenic mice

Soluble amyloid β protein (Aβ)1–40 and highly amyloidogenic Aβ1–42/43 were immunocytochemically labeled in lysosomes of acinar cells and macrophages in the pancreas of transgenic mice systemically expressing a C-terminal fragment of the Aβ precursor. Aβ1–42/43 and long Aβ species extending their C-termini were detected in the detergent-insoluble fraction. Immunoreactivity of cathepsin D was markedly increased in lysosomes filled with Aβ fibrils. These findings indicated that Aβ1–40, Aβ1–42, Aβ1–43 and longer Aβ species were generated in the lysosomes of the transgenic pancreas, and suggested that the activation of cathepsin D, a candidate γ-secretase, leads to acceleration of Aβ amyloid formation.