Prognostic significance of microsatellite instability and Ki-ras mutation type in stage II colorectal cancer

OBJECTIVES: The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival. In the present study we investigated the prognostic significance of two major genetic alterations in CRC: microsatellite instability (MSI+) and the type of Ki-RAS mutation. METHODS: PCR-based molecular techniques were used to screen for MSI+ and Ki-RAS mutation in 396 stage II CRC patients with an average follow-up time of 75 months. Clinicopathological information was obtained by retrospective review of pathology reports. RESULTS: Prominent vascular invasion was identified in 19% of cases and was found to be an independent prognostic factor for poor outcome (relative risk = 2.08, 95% confidence interval: 1.22-3.57, p = 0.008). The MSI+ phenotype was found in 23% of proximal tumours and Ki-RAS mutations in 38% of the overall series. Neither MSI+ nor the type of Ki-RAS mutation showed prognostic significance in this cohort of stage II CRC. CONCLUSIONS: MSI+ and Ki-RAS mutation type are not useful markers for the identification of high-risk stage II CRC patients. Further prospective and/or cohort studies are required to determine whether these molecular changes have predictive value for survival benefit from 5-fluorouracil-based adjuvant chemotherapy.     

BREAST CANCER IN WESTERN AUSTRALIA IN 1989: III. ACCURACY OF FNA CYTOLOGY IN DIAGNOSIS

A population-based study of all cases of breast cancer diagnosed in Western Australia (WA) in 1989 revealed 701 cases of cancer in 692 women. Three hundred and ninety-six (56.5%) of these cancers had fine needle aspiration (FNA) cytology. Forty-three cases were managed non-surgically, on the basis of an FNA diagnosis and without histologic follow up. Of the cases with histological follow-up, 73% received an unequivocal diagnosis of malignancy by FNA, and abnormal cells (atypical, suspicious or malignant diagnoses) were reported in 94.2%. Of the cases, 3.2% were reported as benign and in 2.6% the samples taken were unsatisfactory. There were no false positive cytological diagnoses of malignancy. This study is the first to examine the results of FNA diagnosis of breast cancer from a medical community as a whole, rather than for individual or specialist units; the accuracy of diagnosis was similar for different pathology practices including public and private sector laboratories. Lower absolute sensitivity (the proportion of cases given an unequivocal diagnosis of malignancy) was seen in very small and very large tumours, pure duct carcinoma in situ (DCIS), and invasive lobular carcinoma. False negative rates (the proportion of cases given a benign cytological diagnosis) were very low for all laboratories (0–4.5%) and for all types of carcinoma, and the proportion of unsatisfactory samples was exceptionally low for all laboratories (0–4.5%). The overall figures for accuracy are similar to those reported from other centres in Australasia and overseas, and confirm the effective use of FNA cytology throughout the clinical and pathology community in WA.     

Adolescent social stress and social context influence the intake of ethanol and sucrose in male rats soon and long after the stress exposures

Social instability stress in adolescent rats (SS; postnatal day 30–45, daily 1 hr isolation +new cage partner) alters behavioural responses to psychostimulants, but differences in voluntary consumption of natural and drug rewards are unknown. SS also is associated with an atypical behavioural repertoire, for example reduced social interactions. Here, we investigated whether SS rats differ from control (CTL) rats in ethanol (EtOH) or sucrose intake in experiments involving different social contexts: alone, in the presence of an unfamiliar peer, in the presence of its cage partner, or in competition against its cage partner. SS rats drank more EtOH than CTL rats irrespective of social context, although the effects were driven primarily by those tested soon after the test procedure rather than weeks later in adulthood. SS and CTL rats did not differ in sucrose intake, except in adulthood under conditions of competition for limited access (SS>CTL). Adolescent rats drank more sucrose than adults, in keeping with evidence that adolescents are more sensitive to natural rewards than adult animals. Overall, adolescent SS modified the reward value of EtOH and sucrose, perhaps through stress/glucocorticoids modifying the development of the mesocorticolimbic system.     

Characterization of columnar cell lesions of the breast: immunophenotypic analysis of columnar alteration of lobules with prominent apical snouts and secretions

Columnar cell lesions of the breast are detected with increasing frequency in routine pathology practice, in part as a result of the widespread biopsy of nonpalpable breast abnormalities detected by screening mammography. Immunohistochemical investigation of the lesions in relation to the normal breast or to other breast pathologies is not well characterized, and the malignant potential of this spectrum of lesions has not been examined clinically. In this study, a cohort of 45 breast specimens containing columnar cell lesions, in particular, columnar alteration of lobules with prominent apical snouts and secretions (CAPSS), was investigated for expression of a series of breast tumor biomarkers. Using a semiquantitative immunohistochemical scoring system, up-regulation of estrogen, progesterone, and androgen receptors in CAPSS lesions to levels not significantly different from that in in situ or invasive breast tumors was identified. In four cases where CAPSS within a specimen lacked expression of a steroid hormone receptor, the coexisting in situ or invasive carcinoma also lacked expression of that receptor. In 81% of CAPSS lesions, E-cadherin immunostaining was reduced in isolated foci of cells or was decreased in intensity in all cells within the lesion. Quantitation of Ki-67 immunostaining demonstrated that proliferation of cells within CAPSS lesions was increased, compared with normal breast epithelium, but was lower than that detected in in situ or invasive cancers within the same specimens. Results of these analyses indicate that CAPSS shares immunophenotypic alterations with other premalignant lesions, the clinical implications of which may be investigated using established breast tumor biomarkers.     

Atypical ductal hyperplasia and atypia of uncertain significance in core biopsies from mammographically detected lesions: correlation with excision diagnosis

AIMS: To assess: (1) the prevalence of reporting of atypical ductal hyperplasia (ADH) and intraductal atypia of uncertain significance (AUS) in a series of core biopsies from mammographically detected lesions, (2) the proportion of cases where excision revealed breast carcinoma, and (3) whether any diagnoses should be revised on review. METHODS: Breast core biopsy reports from the Sir Charles Gairdner Hospital Breast Assessment Centre for the years 1999-2000 were retrieved. Slides from cases reported as ADH or AUS were reviewed as well as slides from the excision biopsies. RESULTS: There were 1048 core biopsies from 911 women. Breast carcinoma was diagnosed in 197 samples (18.8%) including 88 with invasive carcinoma (8.4%), 109 with ductal carcinoma in situ (DCIS) (10.4%). Three biopsies (0.3%) 'suspicious' of invasive carcinoma proved to be so. Of 52 samples (5.0%) with a diagnosis of ADH or AUS, 46 were excised, showing seven invasive carcinomas, 15 DCIS, 11 ADH, two lobular carcinoma in situ (LCIS), nine fibrocystic change (FCC), one mucocoele-like lesion and one fibroadenoma. The 22 malignancies represented 47.8% of the excised lesions. On review, seven of the 52 original core diagnoses were downgraded to benign hyperplasia. Five underwent excision, revealing two FCC, one complex sclerosing lesion, and two incidental lesions unrelated to the mammographic abnormality, including a microscopic tubular carcinoma and a focus of LCIS. In one case reviewed as unsatisfactory, excision showed invasive carcinoma. Lesions of particular interest included a case of high-grade DCIS with local regression in the core biopsy (so-called 'bumt out DCIS'), and one case diagnosed on excision as micropapillary ADH, where the review diagnosis was micropapillary DCIS. CONCLUSIONS: ADH and AUS were reported in 5.0% of biopsies. There was a high rate of carcinoma (47.8%) in subsequent excisions. Very few diagnoses were revised on review. Current protocols for excision of lesions with a 14-gauge core biopsy diagnosis of ADH/AUS appear justified. Literature review suggests that vacuum-assisted core sampling with 11-gauge needles will not remove the need for excision. Further study of local regression of DCIS and micropapillary lesions will be worthwhile.     

A solitary pilar leiomyoma of the trunk

Smooth muscle tumours arising in the skin are divided into angioleiomyomas, genital leiomyomas and pilar leiomyomas. Limited data about solitary leiomyoma are available in the literature. We herein report a case of a 66-year-old man who presented to our department with a slowly progressing cutaneous tumour of the right scapular area that had developed over the past 12 years. Histopathological and immunohistochemical results were consistent with the diagnosis of pilar leiomyoma. Pilar leiomyoma is a benign smooth muscle tumour arising from arrector pili muscle. Tumours can be painful from compression of cutaneous nerves or because of fibre contraction within the tumour in case of cold weather or emotional stress. This case is noteworthy as the piloleiomyoma was solitary, located on the trunk and had an unusual nipple aspect.