Prognostic impact of tumor budding and EMT in periampullary adenocarcinoma: a quantitative approach.

The presence of invasive cell clusters known as tumor budding and the closely related epithelial mesenchymal transition (EMT) have a prognostic impact on cancer patients' overall survival. Interestingly, data quantitatively analyzing and correlating the amount of tumor buds and patient overall survival as well as the impact of expression of epithelial phenotype markers are missing. Periampullary carcinoma samples of 171 patients were immunohistochemically stained for E-Cadherin (ECad). Tumor cell clusters (TCC, defined from one to 50 cells) were manually quantified comprising tumor cell number and subcellular localization of ECad expression (membranous, cytoplasmic or mixed). Data analyses were performed using elastic net feature selection. Hereby, five distinct intervals of TCC sizes and corresponding fractions of cells with distinct ECad expression were identified. Prognostic features of the defined budding categories were entered into a subsequent Cox regression model together with standard clinicopathological parameters and, based on the model prediction, cases were categorized into "low and high budding" grades. Overall median TCC size was 16 cells (range: 2-36 cells). The median number of TCCs per tumor was 42 (range: 3-283). Elastic net feature selection identified TCCs of 6-10 and 31-35 cells as prognostically most relevant negative and positive features, respectively. Regarding ECad expression, cytoplasmic ECad expression in TCCs of 11-15 as well as of 26-30 cells revealed prognostic relevance. Combining TCC numbers and ECad expression, budding grade qualified as independent prognostic factor for patient overall survival (p<0.001) in a multivariable clinicopathologic Cox model. Applying an advanced modelling by machine learning on a cohort of periampullary cancers, we show that not the smallest TCCs (1-5 cells) but tumor cell nests containing 6-10 cells display the strongest negative prognostic relevance. Moreover, we demonstrate that larger TCCs might have a strong positive prognostic impact in periampullary adenocarcinomas, contributing to establishing an advanced grading system.

Hysteroscopic treatment of uterine tumor resembling ovarian sex cord-like tumor (UTROSCT).

The decision to preserve the uterus in a young nulliparous woman with an extremely rare tumor is challenging. Uterine tumor resembling ovarian sex cord-like tumor (UTROSCT) belongs to the rarest uterine pathologies. A 22-year-old nulligravida with uterine bleeding underwent a hysteroscopic resection of an intrauterine mass presumed as grade-1 submucous myoma. According to the presence of sex cord-like differentiation and positivity for calretinin, CD99, estrogen receptor, vimentin, WT1 and Melan-A, the tumor was diagnosed as UTROSCT. After 28 months, without any adjuvant therapy, the patient is still free of recurrence. This is the youngest patient with UTROSCT reported so far, with the longest follow-up among all five cases treated via hysteroscopy. Although UTROSCT has been traditionally treated with hysterectomy (with or without bilateral salpingo-oophorectomy), no established treatment protocol for UTROSCT exists. UTROSCT shows a low-malignant potential, but metastasizing and recurrent cases occur. In light of the probably less aggressive tumor biology and with respect to the patient's autonomy, a conservative, uterus preserving treatment appears to be justified in selected cases in which close follow-up can be guaranteed. Further case reports are needed to prove the safety of organ-preserving strategy in UTROSCT.

TLR9-dependent and independent pathways drive activation of the immune system by Propionibacterium acnes.

Propionibacterium acnes is usually a relatively harmless commensal. However, under certain, poorly understood conditions it is implicated in the etiology of specific inflammatory diseases. In mice, P. acnes exhibits strong immunomodulatory activity leading to splenomegaly, intrahepatic granuloma formation, hypersensitivity to TLR ligands and endogenous cytokines, and enhanced resistance to infection. All these activities reach a maximum one week after P. acnes priming and require IFN-γ and TLR9. We report here the existence of a markedly delayed (1-2 weeks), but phenotypically similar TLR9-independent immunomodulatory response to P. acnes. This alternative immunomodulation is also IFN-γ dependent and requires functional MyD88. From our experiments, a role for MyD88 in the IFN-γ-mediated P. acnes effects seems unlikely and the participation of the known MyD88-dependent receptors, including TLR5, Unc93B-dependent TLRs, IL-1R and IL-18R in the development of the alternative response has been excluded. However, the crucial role of MyD88 can partly be attributed to TLR2 and TLR4 involvement. Either of these two TLRs, activated by bacteria and/or endogenously generated ligands, can fulfill the required function. Our findings hint at an innate immune sensitizing mechanism, which is potentially operative in both infectious and sterile inflammatory disorders.

MAGE qPCR improves the sensitivity and accuracy of EBUS-TBNA for the detection of lymphatic cancer spread.

INTRODUCTION: Microscopic examination of histologic slides or cytologic specimens of mediastinal lymph node samples obtained by diagnostic mediastinoscopy or endobronchial ultrasound-guided fine-needle aspiration (EBUS-TBNA) is routinely used for the staging of lung cancer patients. Therefore, we explored whether the detection of tumor-associated mRNA in lymph node samples from patients with suspected lung cancer adds diagnostic accuracy to conventional histopathological staging. METHODS: We examined 202 lymph nodes obtained by EBUS-TBNA or mediastinoscopy from 89 patients with lung cancer. Lymph node samples from patients with nonmalignant disease were available as controls (60 samples from 31 patients). Real-time quantitative mRNA analysis was performed for melanoma antigen-A genes (MAGE-A 1-6, MAGE-A 12) using a LightCycler 480 instrument. RESULTS: MAGE transcript levels in control and cancer patients differed widely, and the 95% confidence interval served to define the threshold between negative and positive samples. MAGE 1 to 6 transcripts were detected in 35 of 122 (28.7%) lymph nodes obtained by EBUS-TBNA and 16 of 80 (20.0%) lymph nodes obtained by mediastinoscopy. MAGE 12 transcripts were detected in 10 of 122 (8.2%) lymph nodes obtained by EBUS-TBNA and 9 of 80 (11.3%) lymph nodes obtained by mediastinoscopy. Although the accuracy of histopathological diagnosis after EBUS-TBNA and mediastinoscopy was 69.6% and 84.1%, respectively, it increased to 81.2% and 86.4%, respectively, when combined with MAGE-quantitative polymerase chain reaction. CONCLUSIONS: The combination of EBUS-TBNA and MAGE-quantitative polymerase chain reaction increases the accuracy of tumor cell detection to the level seen with mediastinoscopy.

Effective targeting of prostate cancer by lymphocytes redirected by a PSMA × CD3 bispecific single-chain diabody.

BACKGROUND: For redirecting T-lymphocytes to induce prostate cancer cell lysis, we constructed a novel bispecific single-chain (bsc) diabody directed to the prostate specific membrane antigen (PSMA) and the T-cell receptor (TCR)-associated CD3 molecule on T-cells. METHODS: The PSMA × CD3 bsc diabody was generated from an anti-CD3 single chain Fv fragment (scFv) and the anti-PSMA scFv D7. It was expressed in E. coli and purified from the periplasmic extract and culture supernatant by immobilized metal affinity chromatography (IMAC). The binding properties were tested on PSMA-expressing prostate cancer cells and PSMA-negative cell lines as well as on Jurkat cells by flow cytometry. For in vitro functional analysis, a cell viability test (WST-1) was used and activation of T-cells was determined by measuring the surface marker expression of CD25 and CD69. For in vivo evaluation, the diabody was administered in combination with human peripheral blood lymphocytes (Ly) in a C4-2 xenograft-SCID mouse model. RESULTS: Specific binding of the PSMA × CD3 bsc diabody both to CD3-positive Jurkat cells and PSMA-expressing C4-2 cells was shown by flow cytometry. In vitro, the PSMA × CD3 bsc diabody proved to be a potent agent for retargeting CD4+ and CD8+ human lymphocytes to lyse C4-2 prostate cancer cells. Treatment of SCID mice bearing C4-2 tumor xenografts with the diabody and human lymphocytes efficiently inhibited tumor growth. CONCLUSIONS: The PSMA × CD3 bsc diabody bears a high potential for the immunotherapy of prostate cancer.

Performance of the Aptima high-risk human papillomavirus mRNA assay in a referral population in comparison with Hybrid Capture 2 and cytology.

This study compared the Aptima human papillomavirus (HPV) (AHPV; Gen-Probe Incorporated) assay, which detects E6/E7 mRNA from 14 high-risk types, the Hybrid Capture 2 HPV DNA (HC2; Qiagen Incorporated) test, and repeat cytology for their ability to detect high-grade cervical lesions (cervical intraepithelial neoplasia grade 2+ [CIN2+]) in women referred to colposcopy due to an abnormal Papanicolaou (Pap) smear. A total of 424 clinical specimens, stored in liquid-based cytology (LBC) vials at room temperature for up to 3 years, were tested by repeat cytology, the AHPV assay, and the HC2 test. Assay results were compared to each other and to histology results. The overall agreement between the AHPV assay and the HC2 test was 88.4%. The sensitivity (specificity) of cytology, the HC2 test, and the AHPV assay for the detection of CIN2+ was 84.9% (66.3%), 91.3% (61.0%), and 91.7% (75.0%) and for the detection of CIN3+ was 93.9% (54.4%), 95.7% (46.0%), and 98.2% (56.3%), respectively. Of the disease-positive specimens containing high-risk HPV (HR HPV) DNA as determined by Linear Array (Roche Diagnostics), the AHPV assay missed 3 CIN2 and 1 microfocal CIN3 specimen, while the HC2 test missed 6 CIN2, 4 CIN3, and 1 cervical carcinoma specimen. The AHPV assay had a sensitivity similar to but a specificity significantly higher (P < 0.0001) than the HC2 test for the detection of CIN2+. The AHPV assay was significantly more sensitive (P = 0.0041) and significantly more specific (P = 0.0163) than cytology for the detection of disease (CIN2+).

Innate, antigen-independent role for T cells in the activation of the immune system by Propionibacterium acnes.

Propionibacterium acnes is a human commensal but also an opportunistic pathogen. In mice, P. acnes exerts strong immunomodulatory activities, including formation of intrahepatic granulomas and induction of LPS hypersensitivity. These activities are dependent on P. acnes recognition via TLR9 and subsequent IL-12-mediated IFN-gamma production. We show that P. acnes elicits IL-12p40 and p35 mRNA expression in macrophages, and IFN-gamma mRNA in liver CD4(+) T cells and NK cells. After priming with P. acnes, CD4(+) T cells serve as the major IFN-gamma mRNA source. In the absence of CD4(+) T cells, CD8(+) T cells (regardless of antigenic specificity) or NK cells can produce sufficient IFN-gamma to induce the P. acnes-driven immune effects. Moreover, in the absence of alpha beta T cells, gamma delta T cells also enable the development of strongly enhanced TNF-alpha and IFN-gamma responses to LPS and intrahepatic granuloma formation. Thus, under microbial pressure, different T-cell types, independent of their antigen specificity, exert NK-cell-like functions, which contribute decisively to the activation of the innate immune system.

Performance of p16INK4a-cytology, HPV mRNA, and HPV DNA testing to identify high grade cervical dysplasia in women with abnormal screening results.

OBJECTIVE: The prognostic value of dysplastic lesions of the uterine cervix cannot be adequately determined by Pap cytology alone. Detection of HPV DNA increases the diagnostic sensitivity. However, due to the very high prevalence of transient HPV infections, HPV DNA testing suffers from poor diagnostic specificity. Biomarkers that highlight the shift from self limited transient to potentially dangerous transforming HPV infections may improve the accuracy of cervical cancer screening. We evaluated HPV E6/E7 mRNA detection (APTIMA), p16(INK4a)-immunocytology (CINtec), and HPV DNA testing (HC2) to identify women with high grade cervical neoplasia in a disease-enriched cross-sectional cohort. METHODS: Liquid based cytology specimens were collected from 275 patients. All assays were performed from these vials. Detection rates of each test were evaluated against conventional H&E based histopathology alone and stratified by p16(INK4a)-immunohistochemistry (IHC). RESULTS: All assays yielded a high sensitivity for the detection of CIN3+ (96.4% (95% CI, 90.4-98.8) for HC2, 95.5% (89.2-98.3) for APTIMA and CINtec) and CIN2+ (91.5% (85.8-95.1) for HC2, 88.4% (82.3-92.7) for APTIMA, 86.6% (80.2-91.2) for CINtec). The specificity to detect high grade dysplasia was highest for CINtec p16(INK4a)-cytology (60.6% (52.7-68.0) in CIN3+ and 74.8% (65.5-82.3) in CIN2+), followed by APTIMA (56.4% (48.4-64.0) in CIN3+ and 71.2% (61.7-79.2) in CIN2+) and HC2 (49.1% (41.3-56.9) in CIN3+ and 63.4% (53.7-72.1) in CIN2+). All tests had higher sensitivity using p16(INK4a)-IHC-positive CIN2+ lesions as endpoint. CONCLUSIONS: Biomarkers that detect HPV induced dysplastic changes in the transforming stage are promising tools to overcome the current limitations of cervical cancer screening.

Primary prostate cancer cultures are models for androgen-independent transit amplifying cells.

Numerous efforts exist for developing primary prostate cancer cultures for studying the biology of this tumor entity and for evaluation of the effectiveness of novel therapies. However, there is doubt if cultures that represent the fully differentiated phenotype can be established. The aim of the present study was to characterize primary outgrowing prostate epithelial cells due to their basal or luminal characteristics and their potential for serving as androgen-responsible model. From fresh prostate cancer radical prostatectomy specimens, pieces of approximately 2-4 mm diameter were placed on top of transwell culture chambers, which were coated with matrigel and cultured in prostate epithelial selection medium with 10% fetal calf serum. The monolayer of outgrowing cells was incubated with a physiological concentration of 1 nM dihydrotestosterone (DHT). One group was additionally cultivated without DHT and another group was treated with the 5-alpha-reductase-inbitors MK-368 and MK-905. From the monolayer of the outgrowing cells, RNA was isolated and the expression of androgen receptor (AR), prostate-specific antigen (PSA), Kallikrein 2 (KlK2), prostate-specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA), cytokeratin (CK)5, and CK18 was determined by realtime quantitative PCR. The outgrowing cells from the prostate cancer tissue pieces could be characterized as epithelial cells with basal and transit amplifying characteristics as shown by co-expression of CK5 and CK18. In all cultures, a very low expression of the luminal cell marker genes AR, PSA and KLK2 was measured. The levels of PSCA were clearly higher with a broad variation. Upon cultivation without DHT or treatment with alpha-reductase inhibitors no regulation of AR, PSA and KlK2 was found. Due to the co-expression of basal and luminal marker genes, primary prostate cancer cultures can be charaterized as models of transit amplifying cells of the prostatic epithelium. They do not represent the differentiated secretory androgen-responsive cell phenotype.

Three conformational antibodies specific for different PSMA epitopes are promising diagnostic and therapeutic tools for prostate cancer.

BACKGROUND: The prostate specific membrane antigen (PSMA) represents an attractive antigen for antibody-based diagnostic and therapeutic intervention in prostate cancer, since it is highly restricted to the prostate and overexpressed in all tumor stages. The present work describes the in vitro characterization of the three anti-PSMA monoclonal antibodies (mAbs) 3/A12, 3/E7, and 3/F11 in comparison to the mAb J591. METHODS: The mAbs were tested for saturation and competitive binding on C4-2 prostate cancer cells by flow cytometry. Immunohistochemical staining was conducted on frozen prostate normal and cancer tissues as well as on lymph node metastases. Similarly, potential crossreactivities were tested on a broad panel of human normal tissues. RESULTS: The anti-PSMA mAbs showed a strong binding to C4-2 cells with mean half-maximal saturation concentrations of about 14 nM for 3/A12, 17 nM for 3/E7, 9 nM for 3/F11, and 16 nM for J591. Competitive binding studies revealed that our three mAbs bind to different extracellular PSMA epitopes. The mAbs showed comparable staining of epithelial cells for all tested normal and tumorous prostate tissues. Extraprostatic staining was observed on secretory cells of the salivary glands and on the brush border of the duodenal columnar epithelium. J591 additionally showed positive staining of the normal breast epithelium. CONCLUSIONS: Due to their specific binding characteristics, the anti-PSMA mAbs 3/A12, 3/E7, and 3/F11 show great promise for diagnostic and therapeutic applications in prostate cancer.

Post-irradiation pericardial malignant mesothelioma: an autopsy case and review of the literature.

We report a case of a malignant pericardial mesothelioma of the epithelioid type in a 39-year-old man. He had a history of nodular sclerosing Hodgkin's disease treated with irradiation of the cervical and mediastinal regions 24 years before, and of infarction of the anterior wall of the left ventricle, after which a percutaneous coronary intervention was carried out 7 years previously. He was admitted to a cardiology unit with progressive dyspnea. On examination, a hemorrhagic pericardial fluid collection of 600 ml was detected which was successfully drained. On the next day, the patient developed an electromechanical dissociation suggesting a pericardial tamponade, which was followed by circulatory arrest. At autopsy, the pericardial sac was found to contain 300 ml of partly clotted blood. The epicardial surface showed a diffuse thickening, suggesting a chronic fibrous pericarditis without a macroscopically evident distinct tumor mass. A rupture measuring 0.4 cm in diameter was detected in the right ventricular free wall, 1 cm below the level of the tricuspid valve. The diagnosis of a diffusely growing, malignant mesothelioma of the epithelioid type was made on the basis of histological and immunohistochemical examination of the thickened pericardium.

Report of rare bilateral nasolabial cysts.

PURPOSE: Nasolabial cysts are usually unilateral and are quite rare, while bilateral cysts are even rarer. PATIENT AND METHOD: Our report concerns a 48-year-old female with bilateral nasolabial cysts. After many years of misdiagnosis she was finally referred to our clinic with a subnasal swelling of unknown origin. RESULT: Evaluation of the patient's medical history, clinical examination and of a previous CT scan led to the diagnosis of a nasolabial cyst, which was later confirmed by histological examination. Treatment involved the surgical excision. CONCLUSION: A complete surgical excision is recommended using a sublabial approach as the treatment of choice, although transnasal endoscopic marsupialization seems to be a simple and effective alternative. It has been shown that after successful marsupialization, the nasolabial cyst is converted to an air-containing paranasal sinus.

Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivity.

Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12Rbeta2-deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12-independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) beta2, or both, we show that the concomitant absence of TLR4 and IL-12Rbeta2, but not the absence of TLR4 or IL-12Rbeta2 alone, prevented DC-mediated sensitization, generation of effector T cells, and the subsequent CHS response to 2,4,6-trinitro-1-chlorobenzene (TNCB), oxazolone, and fluorescein isothiocyanate. Introduction of the TLR4 transgene into the TLR4/IL-12Rbeta2 mutant restored the CHS inducibility, showing a requirement for TLR4 in IL-12-independent CHS induction. Furthermore, the concomitant absence of TLR2 and TLR4 prevented the induction of CHS to TNCB in IL-12-competent mice. Finally, CHS was inducible in germ-free wild-type and IL-12Rbeta2-deficient mice, but not in germ-free TLR4/IL-12Rbeta2 double deficient mice, suggesting that the necessary TLR activation may proceed via endogenous ligands.

Expression of p16 in conjunctival intraepithelial neoplasia does not correlate with HPV-infection.

The aim of our study was to identify the frequency of expression of p16(INK4a) (CDKN2A) and HPV (human papilloma virus) in different grades of conjunctival intraepithelial neoplasia (CIN).Twelve specimens including CIN I (2), II (3), III (5), and CIN with beginning invasion (2), as well as 15 control specimens, were stained with antibodies against p16(INK4a) and MIB1. The presence of HPV was examined by PCR.p16 as well as MIB1 were significantly elevated in CIN compared to control specimens (p<0.01) without correlation with the differentiation grade. Only two cases with CIN grade 3 contained HPV 16.As few control specimens also showed increased p16(INK4a) expression, p16(INK4a) seems not to be a very reliable marker for the exact determination of CIN. It could serve as an additional diagnostic tool besides the morphological characterization. Our study suggested that p16(INK4a) elevation is not associated with HPV infection.

Histological and immunohistochemical characterisation of conjunctival graft vs host disease following haematopoietic stem cell transplantation.

BACKGROUND: Conjunctival graft vs host disease (cnGvHD) is a complication of haematopoietic stem cell transplantation, in most cases as part of systemic GvHD. Diagnostic biopsies are commonly collected from bulbar conjunctiva only. The aims of our study were to evaluate whether additional biopsies from the tarsal conjunctiva increase sensitivity upon histopathologic evaluation and to investigate the staining profile for common immunohistochemical markers in cnGvHD. We additionally propose an adaptive histological classification for cnGvHD analogous to Lerner's GvHD skin classification for predicting patient survival. METHODS: Formalin-fixed and paraffin-embedded conjunctival specimens from 23 post-mortem control eyes and 42 patients after haematopoietic stem cell transplantation (HSCT) were stained with haematoxylin and eosin (HE), periodic acid-Schiff (PAS) stain and with antibodies against CD1a, CD4, CD8, CD25, CD45RO, CD68, Fas ligand, TIA-1, HLA-DRalpha by means of immunohistochemistry. Cell counting took place in ten representative fields at 64.4 microm (length) x 21.2 microm (width). Multifactorial analysis of variance was performed to assess any influence of cnGvHD on the staining pattern for the immunohistochemical markers. Survival times were estimated by the Kaplan-Meier method. RESULTS: All 42 specimens and none of the controls were diagnosed as cnGvHD. The bulbar specimens were staged according to the modified Lerner classification: grade (G) I: 0; G II: 17 (tarsal with GII, 8); G III: 12 (tarsal with GIII: 1); G IV: 12 (tarsal with G

Surfactant protein A detection in large cell carcinoma of the lung.

Large cell carcinomas of the lung are undifferentiated malignant epithelial tumors that lack cytologic features of small cell carcinoma, glandular cell carcinoma, or squamous cell differentiation. Lung surfactant protein A (SP-A) is produced by alveolar type II cells and Clara cells. Most bronchioloalveolar carcinomas of the lung react positively for SP-A. Positive SP-A staining of large cell carcinoma of the lung could indicate that at least part of these tumors have the same cellular origin or differentiation as bronchioloalveolar carcinoma. The authors determined the SP-A staining of 63 large cell carcinomas of the lung by IHC. In 20 of the 63 (32%), the tumors stained positive for SP-A. This may imply that about one third of large cell carcinomas of the lung have a similar cellular origin or differentiation as bronchioloalveolar carcinoma. The significance of this finding for prognosis and new forms of treatment remains to be determined.

Expression of p63 in conjunctival intraepithelial neoplasia and squamous cell carcinoma.

BACKGROUND: p63 is a homologue of the tumour suppressor gene p53, which is expressed in human basal squamous epithelium. Some investigators maintain that p63 plays a role in the development of squamous epithelium and, despite its homology to p53, it is considered to act as an oncogene. This study investigated the expression of p63 in conjunctival intraepithelial neoplasia of different grades, and conjunctival squamous cell carcinoma and its correlation to the proliferation marker MIB-1. MATERIAL AND METHODS: Seventeen conjunctival specimens excised with the suspicion of either conjunctival intraepithelial neoplasia (CIN) or squamous cell carcinoma were diagnosed histologically as follows: 2 squamous cell carcinomas of the conjunctiva, 2 CIN grade I, 3 CIN grade II, 7 CIN grade III, 2 CIN with beginning invasion and 1 normal conjunctiva with no dysplasia. Sixteen microscopically-normal postmortem conjunctival specimens and normal conjunctiva, CIN and carcinoma specimens were stained immunohistochemically with antibodies against p63 and MIB-1. At least 500 cells per specimen were counted and the percentage of positively-stained cells of each antibody was calculated. RESULTS: A mean of 80% (57-89%) of the dysplastic cells from the CIN specimens stained positively with antibodies against p63, especially in the lower two-thirds of the epithelium, statistically significantly more compared with the normal specimens (9-55%, mean 36%, p<0.001). Nevertheless, we did not find a correlation between the percentage of p63-positive cells and the differentiation grade of the malignant specimens. MIB-1 positivity was shown by 0-1% of the cells in the normal postmortem controls, by 3-30% (mean 12%) of the cells in the basal and occasionally in the middle layer of the CIN specimens, and 16-61% (mean 23%) in the carcinoma specimens. CONCLUSION: In conjunctival intraepithelial neoplasia and squamous cell carcinoma of the conjunctiva, p63 is preferentially expressed in the immature dysplastic epithelial cells. Its staining does not correlate with MIB-1-expression, and therefore does not appear to be linked to cell proliferation.

Surfactant protein A detection in primary pulmonary adenocarcinoma without bronchioloalveolar pattern.

BACKGROUND: Immunohistochemical studies in human lung carcinoma reported positive staining of tumor cells for surfactant protein A (SP-A), especially in peripheral airway cell carcinoma, which include bronchioloalveolar carcinoma and in some reports also papillary subtypes. OBJECTIVE: The purpose of this study was to determine the SP-A expression in tumor cells of lung adenocarcinoma without a bronchioloalveolar pattern, classified according to the WHO. METHODS: In total, 169 primary adenocarcinomas of the lung (109 acinar, 32 solid with mucin, 24 papillary and 4 mucinous) were examined by immunohistochemistry for SP-A expression. RESULTS: Twenty-five percent of acinar, 38% of papillary and 3% of solid adenocarcinoma with mucin showed a positive intracytoplasmic SP-A reaction of the tumor cells. None of the mucinous adenocarcinomas stained for SP-A. This study included the largest number of acinar adenocarcinomas and solid adenocarcinomas with mucin studied for SP-A. We clearly demonstrated that also primary lung adenocarcinoma without a bronchioloalveolar pattern can express SP-A. A positive staining of hyperplastic type II cells surrounding the tumors or entrapped in the tumor could clearly be differentiated from the SP-A-positive stain of tumor cells. CONCLUSION: These results support the theory that SP-A-producing cells may generate not only bronchioloalveolar and papillary carcinoma, but also other subtypes of lung adenocarcinoma.

Reactive alveolar epithelium in chondroid hamartoma of the lung.

OBJECTIVE: To determine the morphologic characteristics of the nonciliated epithelium found in chondroid hamartoma of the lung. STUDY DESIGN: The morphologic characteristics and immunohistochemical reaction for surfactant protein A of the nonciliated epithelium in chondroid hamartoma of the lung was studied by immunohistochemistry. Alveolar epithelium in normal lung tissue and lung tissue surrounding primary lung cancer or metastatic lung lesions was used as a control. RESULTS: In all cases, the nonciliated epithelium in chondroid hamartoma showed the morphologic criteria of hyperplastic alveolar type II cells and a very strong positive surfactant protein A reaction in the cytoplasm when compared with alveolar epithelium of the normal lung. Similar hyperplastic type II cells were also found in the alveolar lung around metastatic or primary lung tumors. CONCLUSION: These findings may indicate that the nonciliated cells found in chondroid hamartoma of the lung are hyperplastic type II cells. This suggests that the alveolar epithelium found in chondroid hamartoma of the lung is a secondary reaction around the hamartoma and not a primary component of the lesion.