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Breast carcinoma-induced angiogenesis helps meet growing metabolic needs of tumors and progressively increases with malignant transformation of benign ducts to ductal carcinoma in situ (DCIS) and ductal carcinoma in situ to invasive carcinoma. There are conflicting data regarding the difference in angiogenesis in low-, intermediate-, and high-grade ductal carcinoma in situ. If angiogenesis is related to ductal carcinoma in situ progression, the types of ductal carcinoma in situ with more aggressive biologic potential would have different vascular patterns than the less aggressive ones. In this study, we classified 51 cases of ductal carcinoma in situ as low (10-20 years to progression to invasive carcinoma), moderate, or high aggressive (2-5 years to progression to invasive carcinoma), based on criteria outlined by Tsikitis and Chung (Am J Clin Oncol 2006; 29:305), which takes into account nuclear grade, mitotic rate, Ki-67, Her2Neu, P53, estrogen, and progesterone receptor expression. We correlated these 3 groups of ductal carcinoma in situ with the extent of periductal and stromal vascularity and the presence and type of vascular breaks. No association of aggressive biologic behavior of ductal carcinoma in situ with any vascular pattern was found. Moreover, no correlation was found between vascular patterns and classifiers of aggressiveness, microvascular density, or outcome (local recurrence, invasive carcinoma, or metastatic disease). To validate our cohort, we confirmed expected correlations of all measured parameters of aggressiveness by correlating them with each other. In summary, vascular patterns in ductal carcinoma in situ do not correlate with the predictors of aggressive behavior, suggesting that the biologic potential of ductal carcinoma in situ is independent of angiogenesis.

Ductal carcinoma in situ (DCIS), a known precursor lesion of invasive cancer of the female breast, is surrounded by a thick basement membrane and a layer of myoepithelial cells. For DCIS to become invasive, both these barriers must be breached by cancer cells. It has been repeatedly suggested that proteolytic enzymes are somehow involved in this process but a direct proof of this event has never been provided. It is our hypothesis that invasion of the DCIS by capillary vessels derived from the periductal necklace of vessels is the most likely mechanism of breaching the basement membrane, providing an escape hatch for cancer cells. This hypothesis was initially tested on ten randomly selected cases of DCIS, with or without invasion. Capillary vessels were visualized by staining histologic sections with an antibody to CD 34 and, in three cases, by combined stain for CD 34 and collagen IV. In five of the 10 cases of DCIS, the presence of discrete capillary vessels invading DCIS could be documented. In two of these five cases, the vessels subdivided the cancerous ducts into territories of unequal sizes. Vascular invasion of DCIS is a plausible mechanism of breaching the basement membrane in DCIS as a prelude to invasion. This hypothesis must be further tested on a much larger number of cases. The hypothesis, if confirmed, may suggest that invasive cancer derived from DCIS may be prevented by antiangiogenic therapy.

Integrins mediate cell adhesion to extracellular matrix and stimulate signals involved in cell proliferation, survival, and migration. Focal adhesion kinase (FAK) is considered the central molecule in integrin-mediated signaling. Previously, FAK has been implicated in invasive tumor behavior based on Northern or Western blot (immunoblot) using total tumor tissue homogenates. We used immunohistochemistry to demonstrate FAK expression in benign cervical epithelium, dysplasia, carcinoma in situ (CIS), and invasive cervical squamous cell carcinomas (SCCs), as well as in benign breast tissue, atypical ductal hyperplasia, and ductal carcinoma in situ (DCIS) and invasive carcinomas of the breast. We also used polymerase chain reaction to analyze whether infection with the high-risk human papillomavirus (HPV) subtypes correlated with FAK overexpression in CIS of the cervix. We found minimal FAK expression in benign cervical and breast epithelium and in low-grade squamous dysplasia (CIN I and CIN I-II) of the cervix, and variable FAK expression in CIS lesions of the cervix (10 of 14 cases). Most of the invasive SCCs of the cervix (13 of 16 cases) and DCIS of the breast (6 of 8 cases) were positive for FAK. Surprisingly, all DCIS of the breast were also strongly positive (7 of 7). Only 3 of 13 cases of atypical ductal hyperplasia were focally positive for FAK. Regardless of the intensity of FAK staining, all CIS of the cervix were positive for either HPV 16 or 18. We conclude that FAK overexpression is not restricted to invasive phenotype, but rather appears to be a marker for malignant transformation.

The results of mapping of the urinary bladder are reported and discussed. It has been shown that Brunn's nests, cystitis cystica, and the vaginal type of squamous metaplasia are commonly found in normal bladders and thus cannot be considered as precancerous lesions. Mapping of cancerous bladders and related histologic and clinical observations strongly suggests that there are two distinct pathways in bladder neoplasia: the papillary pathway and the nonpapillary pathway. Papillary tumors with thin stalks must be considered as a focal expression of the proliferative potential of the urothelium. They are per se quite harmless but may be followed by other manifestations of neoplasia. Broad based papillary tumors, regardless of grade, may have "pushy borders," which extend into the lamina propria but rarely invade the muscularis. Nonpapillary flat lesions, notably atypical hyperplasia and carcinoma in situ, appear to be the principal source of invasive and metastasizing bladder cancer. The presence of the flat lesions puts the patient at high risk for the development of invasive carcinoma. Methods of assessment of the cancerous bladder are suggested and discussed.

Digital images acquired by high resolution scanning of urothelial cells are segmented into nuclear and cytoplasmic regions. A method which is a hybrid of a gradient tracking method and a thresholding method is used, and criteria are presented to automatically detect failures of the algorithm. Tests on a sample of benign and malignant urothelial cells show a significant improvement in both accuracy and reliability as compared with a single segmentation method.

Established cell lines derived from human urinary bladder carcinomas produce heat-stable alkaline phosphatase [orthophosphoric-monoester phosphohydrolase (alkaline optimum), EC 3.1.3.1] which resembles the oncofetal enzyme of HeLa S3. Rat bladder cancer cell lines derived from chemically induced tumors produce heat-labile alkaline phosphatase. Corticosteroids and/or hyperosmolality do not influence the enzyme of rodent cells, but induce increased levels of activity in human cells. The increase is most pronounced when human cells multiply in hyperosmolar medium containing prednisolone. Under these conditions a rise of over 100-fold in specific activity is noted. This synergistic effect, not seen with other cultured heteroploid cells, may represent a specific characteristic of cells derived from human bladder tumors.

The authors summarize the current status of thin-needle aspiration biopsy of the prostate and evaluate the accomplishments and limitations of this method of diagnosis. Historical developments, indications, technique, contraindications, complications, cytology of aspirates, diagnostic efficacy of aspirates, and grading of prostatic carcinomas are discussed.

Complete mapping of epithelium has been performed in 10 bladders surgically removed for cancer. In all cases, in areas adjacent to or distant from the visible tumors, nonpapillary carcinoma in situ and related lesions such as atypical hyperplasia could be demonstrated. More importantly, in 5 of the 10 bladders, areas of occult invasive carcinoma derived from such abnormal epithelia have been recorded. These findings fully confirm prior observations and raise the number of totally mapped bladders to 20. The histologic findings in the entire series of 20 cases are discussed and the distribution of cancer and precancerous lesions tabulated. It is suggested that the areas of the bladder most frequently affected by precancerous lesions are the left and right lateral walls and the posterior wall. The trigone and the dome are less frequently involved. The need for aggressive assessment of bladder epithelium in patients with tumors of the bladder and/or early radical treatment for patients with nonpapillary carcinoma in situ is discussed in light of these observations.

An in situ hybridization technique was applied under stringent conditions to paraffin sections of urethral condylomata from male patients to determine the presence of DNA sequences of human papillomavirus (HPV) types 6, 11, 16, and 18. The material consisted of 15 classical condylomata acuminata, two flat condylomata, and five recurrent lesions. HPV DNA sequences could be identified in all 15 condylomata acuminata; in 13 lesions, two types of viral DNA were observed (types 6 and 11 in 12, types 6 and 18 in one). In the remaining two condylomata acuminata, only HPV type 11 was present. One of the two flat condylomata was negative with all the probes, and one was borderline-positive for HPV 6. Four of five recurrent lesions contained the same types of viral DNA as the primary lesions, albeit with slight differences in the intensity of viral expression. One lesion was negative with all probes. We conclude that urethral condylomata in males contain the same types of HPV as seen in other anogenital lesions of both sexes and that infection with two viral types is common. In situ hybridization with HPV DNA probes is applicable to archival material and therefore may prove to be of value in future epidemiologic studies comparing lesions in sexual partners. The determination of viral type may have therapeutic implications.

The presence of papillomavirus particles was documentd by electron microscopy in atypical squamous epithelium of the cervix, vagina, and vulva, and in cells derived therefrom in four women with compromised immune status who were being followed in our clinics. Three of the patients had treated Hodgkin's disease, and one a dermatologic disorder, perhaps akin to epidermodysplasia verruciformis. Initially, all four patients developed treatment-resistant condylomata acuminata of the vulva and adjacent areas. Subsequently, one of the patients was shown to harbor in the vagina a focus of markedly atypical epithelium, perhaps a flat condyloma. Two other patients, followed for several years, developed multiple epidermoid carcinomas in situ affecting the cervix, vagina, and vulva. In one of these two latter patients the disease progressed to multiple foci of superficially invasive carcinoma. The possible role of the human papillomavirus in the genesis of these lesions is discussed.

Three cases of subareolar florid duct papillomatosis associated with breast cancer were recorded. In two of these, direct transition of the nipple adenoma to duct cancer was documented. In the third case a nipple papilloma was present simultaneously with a separate infiltrating lobular carcinoma in the same breast. The apparent rarity of this association is discussed.

This paper gives an evaluation of the attitudes of dentists in New York City toward a program o f oral cytology screening and of the effectiveness of this technic in oral cancer detection.