Human papillomavirus infection and cervical cytology in HIV-infected and HIV-uninfected Rwandan women.

BACKGROUND: Data on human papillomavirus (HPV) prevalence are essential for developing cost-effective cervical cancer prevention programs. METHODS: In 2005, 710 human immunodeficiency virus (HIV)-positive and 226 HIV-negative Rwandan women enrolled in an observational prospective cohort study. Sociodemographic data, CD4+ cell counts, and cervical specimens were obtained. Cervicovaginal lavage specimens were collected from each woman and tested for >40 HPV types by a polymerase chain reaction assay; HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 were considered primary carcinogenic HPV types. RESULTS: The prevalence of HPV was higher in HIV-positive women than in HIV-negative women in all age groups. Among HIV-infected women, 69% were positive for >or=1 HPV type, 46% for a carcinogenic HPV type, and 10% for HPV-16. HPV prevalence peaked at 75% in the HIV-positive women aged 25-34 years and then declined with age to 37.5% in those >or=55 years old (Ptrend<.001). A significant trend of higher prevalence of HPV and carcinogenic HPV with lower CD4+ cell counts and increasing cytologic severity was seen among HIV-positive women. CONCLUSIONS: We found a higher prevalence of HPV infection in HIV-positive than in HIV-negative Rwandan women, and the prevalence of HPV and carcinogenic HPV infection decreased with age.

Discrepant cytologic and radiographic findings in adjacent galactocele and fibroadenoma: a case report.

BACKGROUND: Clinical, radiologic and pathologic evaluation of a breast mass during pregnancy and lactation often presents a challenge. We report a case of a longstanding benign breast mass that was negative on fine needle aspiration biopsy (FNAB) but sonographically appeared suspicious for carcinoma. CASE: A 41-year-old patient presented with a long-standing benign breast nodule that increased in size postpartum and became painful. The patient was breastfeeding when she developed mastitis in the surrounding area and was treated with antibiotics. The inflammation resolved, but the original mass persisted. FNA of the mass yielded thick, whitish material that on microscopic examination showed clusters of ductal cells with striking reactive, reparative and lactation changes admixed with amorphous material and crystals. The smear pattern was interpreted as negative. However, the sonogram revealed a solid lesion with mixed echogenicity suspicious for malignancy. The patient underwent lumpectomy, which showed concomitant fibroadenoma and galactocele. CONCLUSION: We suspect that in lactating patients preexisting breast masses may interfere with the milk flow, thus rendering the breast tissue around the mass prone to galactocele formation. This may result in erroneous clinical and radiologic impression of growth and transformation of a preexisting lesion.

ARC (apoptosis repressor with caspase recruitment domain) is a novel marker of human colon cancer.

The ability of cells to escape apoptosis is critical for carcinogenesis as well as resistance to radiation and chemotherapy. ARC (Apoptosis Repressor with CARD (caspase recruitment domain)) is an unusual inhibitor of apoptosis in that it antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. ARC is expressed predominantly in terminally differentiated cells such as cardiac and skeletal myocytes and neurons. Recently, however, the abundance of ARC was noted to be markedly increased in the epithelium of primary human breast cancers compared with benign breast tissue and to confer chemo- and radiation-resistance. Whether the induction of ARC is specific to breast cancer or a more general feature of neoplasia remains unknown. In this study, we assessed the abundance and subcellular localization of ARC in 21 human colon cancer cell lines and in 44 primary human colon adenocarcinomas and adjacent benign colonic tissue. ARC was present at high levels in most colon cancer cell lines and in almost all primary colon cancers compared with corresponding controls. Levels of ARC in the cytoplasm were increased in well, moderately, and poorly differentiated cancers compared with benign tissue, while levels of nuclear ARC were increased only in moderately differentiated tumors. Moreover, epithelial cancers of the ovary and cervix exhibited increased ARC abundance compared with controls. These results demonstrate that ARC is a novel marker of human colon cancer and suggest that it may be a general feature of epithelial cancers.

HepPar1, MOC-31, pCEA, mCEA and CD10 for distinguishing hepatocellular carcinoma vs. metastatic adenocarcinoma in liver fine needle aspirates.

OBJECTIVE: To investigate immunohistochemical staining of hepatocyte paraffin-1 (HepPar1), alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen (pCEA), monoclonal CEA (mCEA), MOC-31 and CD10 for differential diagnosis of hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) on fine needle aspiration biopsy (FNAB). STUDY DESIGN: Fifty-one archival, paraffin-embedded FNAB cell blocks, representing 18 HCCs and 33 MAs, were immunostained with antibodies for AFP, CD10, pCEA, mCEA, HepPar1 and MOC-31. RESULTS: HepPar1, AFP, canalicular pCEA and CD10 were positive in 78% (14 of 18), 28% (5 of 18), 72% (13 of 18) and 35% (6 of 17) of cases of HCC, respectively. The 33 MAs were negative for immunostaining of the above antibodies except for one AFP-positive MA. Ninety-seven percent (31 of 32) of the MAs and 6% (1 of 17) of the HCCs were positive for MOC-31. Monoclonal CEA was immunoreactive on 82% (27 of 33) of the MAs and negative on all the HCCs. CONCLUSION: HepPar1 was the most sensitive marker for HCC, followed by canalicular staining for pCEA. For MA, MOC-31 was the most sensitive marker; mCEA was slightly less sensitive but more specific. We suggest using HepPar1, pCEA, CD10, MOC-31 and mCEA as a panel for distinguishing HCC from MA in liver FNAB.

Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor alpha-positive status.

A Japanese study reported that up to 16% of breast cancer samples harbor a sporadic mutation within the human Cav-1 gene, namely P132L. To date, however, no studies have examined the United States' population. Here, we developed a novel allele-specific real-time PCR assay to detect the Cav-1 P132L mutation in mammary tumor cells isolated by laser capture microdissection from formalin-fixed paraffin-embedded breast cancer samples. We report that the Cav-1 P132L mutation is present in approximately 19% of estrogen receptor alpha (ERalpha)-positive breast cancers but not in ERalpha-negative breast cancers. This is the first demonstration that the P132L mutation is exclusively associated with ERalpha-positive mammary tumors. We also identified six novel Cav-1 mutations associated with ERalpha-positive breast cancers (W128Stop, Y118H, S136R, I141T, Y148H, and Y148S). Thus, the overall incidence of Cav-1 mutations in ERalpha-positive breast cancers approaches 35% (greater than one-third). To mechanistically dissect the functional relationship between Cav-1 gene inactivation and ERalpha expression, we isolated primary mammary epithelial cells from wild-type and Cav-1-/- mice and cultured them in a three-dimensional system, allowing them to form mammary acinar-like structures. Under conditions of growth factor deprivation, Cav-1-deficient mammary acini displayed increased ERalpha levels and enhanced sensitivity toward estrogen-stimulated growth, with specific up-regulation of cyclin D1. Finally, we discuss the possibility that sporadic Cav-1 mutations may act as an initiating event in human breast cancer pathogenesis.

ErbB3-dependent motility and intravasation in breast cancer metastasis.

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin beta1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth.