CDKN1C/p57kip2 Is a Candidate Tumor Suppressor Gene in Human Breast Cancer

BACKGROUND. CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. METHODS. We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. RESULTS. AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2–60% of paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20 (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and 5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss of CDKN1C expression from myoepithelial layer cells, which stained intensely in 17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast, luminal cells displayed less intense, focal staining fairly consistently across histologies. Decreased CDKN1C was not clearly associated with tumor grade, histology, ER, PR or HER2 status. CONCLUSION. CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.Department of Defense Breast Cancer Research Program (DAMD 17-99-1-9573); National Institutes of Health PHS (CA081078); LaPann Fun

Estudio comparativo cito-histológico de las enfermedades prostáticas

Este trabajo fue realizado para evaluar la validez diagnostica y pronostica de la aspiración transrectal con aguja fina de la próstata. Con este objetivo 345 aspiraciones procedentes de 289 enfermos fueron evaluadas y comparadas a los correspondientes diagnósticos histológicos. Un 61% de los casos sospechosos citologicamente recibieron el diagnóstico histológico de adenocarcinoma. La capacidad citológica para determinar el grado de diferenciación de los tumores prostáticos fue evaluada comparando los resultados obtenidos al clasificar histologicamente el grado de diferenciación utilizando los criterios expuestos por A. Bocking. Al evaluar separadamente los distintos aspectos cinológicos el incremento del tamaño nucleolar obtuvo la mayor concordancia (69%) después seguía el incremento del tamaño nuclear (53%). El material cinológico restante fue usado para determinar el contenido en dna nuclear que en los enfermos con procesos prostáticos benignos resulto ser diploide con poblaciones celulares aneuploides siempre menor del 2%. En 3 de los 5 enfermos con adenocarcinoma bien diferenciado el porcentaje de células aneuploides vario entre el 16 y el 60%. El porcentaje de células aneuploides en los adenocarcinomas pobremente diferenciados y metastásicos fue siempre superior al 72% con la excepción de un solo caso con un 55%. Se concluye que la aspiración transrectal con aguja fina de la próstata es un método libre de complicaciones clínicas fácil y simple de utilizar que permite el diagnostico temprano de carcinomas y que al completarse con flujocitometría permite predecir el comportamiento biológico de los casos malignos

Early detection of high-grade squamous intraepithelial lesions in the cervix with quantitative spectroscopic imaging

Quantitative spectroscopy has recently been extended from a contact-probe to wide-area spectroscopic imaging to enable mapping of optical properties across a wide area of tissue. We train quantitative spectroscopic imaging (QSI) to identify cervical high-grade squamous intraepithelial lesions (HSILs) in 34 subjects undergoing the loop electrosurgical excision procedure (LEEP subjects). QSI’s performance is then prospectively evaluated on the clinically suspicious biopsy sites from 47 subjects undergoing colposcopic-directed biopsy. The results show the per-subject normalized reduced scattering coefficient at 700 nm (A[subscript n]) and the total hemoglobin concentration are significantly different (p<0.05) between HSIL and non-HSIL sites in LEEP subjects. A[subscript n] alone retrospectively distinguishes HSIL from non-HSIL with 89% sensitivity and 83% specificity. It alone applied prospectively on the biopsy sites distinguishes HSIL from non-HSIL with 81% sensitivity and 78% specificity. The findings of this study agree with those of an earlier contact-probe study, validating the robustness of QSI, and specifically A[subscript n], for identifying HSIL. The performance of A[subscript n] suggests an easy to use and an inexpensive to manufacture monochromatic instrument is capable of early cervical cancer detection, which could be used as a screening and diagnostic tool for detecting cervical cancer in low resource countries.National Institutes of Health (U.S.) (Massachusetts Institute of Technology. Laser Biomedical Research Center Grant R01 CA097966)National Institutes of Health (U.S.) (Massachusetts Institute of Technology. Laser Biomedical Research Center Grant P41 RR02594

<it>CDKN1C</it>/p57^kip2is a candidate tumor suppressor gene in human breast cancer

Abstract Background CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor previously implicated in several types of human cancer. Its family members (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C may be involved in human breast carcinogenesis in vivo. Methods We determined rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real-time PCR (qPCR), and the CDKN1C protein level in 20 cancers using immunohistochemistry (IHC). All samples were obtained using laser microdissection. Data were analyzed using standard statistical tests. Results AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA levels were reduced in 9/10 (90%) cancers (p Conclusion CDKN1C is expressed in normal epithelium of most breast cancer cases, mainly in the myothepithelial layer. This expression decreases, at both the mRNA and protein level, in the large majority of breast cancers, and does not appear to be mediated by AI/LOH at the gene. Thus, CDKN1C may be a breast cancer tumor suppressor.</p