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Background: To determine the frequency of squamous cell change associated with endometrial carcinoma, to evaluate the relationship between squamous cell change and clinicopathological features, and to assess cytological findings for squamous cells with and without nuclear atypia in endometrial smears., Methods: In 103 cases of endometrioid adenocarcinoma of the endometrium having both histological and cytological specimens, the frequencies and relationships between the presence and absence of squamous cell changes were evaluated, as were the clinicopathological features of such changes. In endometrial smears, squamous cells with and without nuclear atypia were clinicopathologically assessed., Results: Squamous cell changes were found in 58.3% of cases that had both histological and cytological preparations. There were no significant differences between the group with squamous cell changes and the group without in any of the clinicopathological features. In the cytological smears, 70.0% of the 60 cases that showed squamous cell changes in both preparations did not have nuclear atypia of squamous cells, while 30.0% of those cases had atypia. The group of cases with squamous cells without atypia tended to be better differentiated than the group with atypia. Vessels were permeated significantly more often in the group with atypia than in the group without., Conclusions: Our data suggest the importance of observing squamous cells in endometrial cytology, especially concerning findings on nuclei with vs without atypia, when endometrial carcinoma is suspected., (© 2015 Wiley Periodicals, Inc.)

Objective: We previously reported on the classification of the nuclear chromatin distribution into 3 types, that is peripheral (P), mixed (M) and central (C), which were related to the malignancy of cervical glandular lesions. However, the classification was subjective as it was performed by visual assessment. In the present study, quantitative assessment of nuclear chromatin distribution using image analysis by computer was applied for objective classification of cervical squamous epithelial lesions, which are the most common cervical lesions., Study Design: A total of 130 cells (44 cells of type P, 78 of type M and 8 of type C) from cytological specimens of cervical squamous epithelial lesions (dysplasia, squamous cell carcinoma) were analyzed. An image analysis program was developed as a plug-in macro program of an existing image processing software. The radial distribution (RD) value, which represents the gradient of the staining intensity from the center to the edge of a nucleus, was defined as an index of the chromatin distribution., Results: The RD values calculated in type P, type M and type C cells showed significant statistical differences as assessed by the t test (p < 0.001)., Conclusions: Quantification of the nuclear chromatin distribution by image analysis is fast and highly objective. The RD value could be useful as an index for malignancy., (Copyright © 2011 S. Karger AG, Basel.)

The clinical and histologic findings in five cases of endometrial cancer, which developed following radiation therapy for squamous cell carcinoma of the cervix, are described. The mean age at endometrial cancer diagnosis was 69 years and average latency period from initial therapy to development of endometrial carcinoma was 13.4 years. For endometrial cancer, one patient had Stage Ib, one patient had Stage IIIa, two patients had Stage IIIc, and one patient did not undergo laparotomy. The histological types were carcinosarcoma in two patients, endometrioid adenocarcinoma, grade 3 in one patient, and clear cell carcinoma in one patient. All patients died of disease within 33 months of diagnosis. Endometrial cancers that develop after radiation treatment have a preponderance of high-risk histological subtypes, and consequently have a poor prognosis. Long-term follow-up should be mandatory for patients surviving radiation therapy for cervical cancer in order to detect and effectively treat second malignancies.

Background: Although the usefulness of the antimicrobial peptides known as defensins has been suggested against oral and skin infections, possible adverse effects of the defensins on the host should be understood before clinical applications can be contemplated., Objective: In the present study, we investigated how alpha-defensin (HNP-1) and beta-defensins (hBD-1, -2, -3) affect cells including primary epithelial cells, fibroblasts and squamous cell carcinoma cell lines, SCC-9 and KB., Method: Cell proliferation was assessed by the direct cell counting and XTT assay., Results: We found that alpha-defensin promotes proliferation of the epithelial cells at low concentration but has a cytotoxic effect at high concentration. In contrast, beta-defensins have little effect on these cells at any concentration, suggesting that beta-defensins may have no adverse effects on the host., Conclusion: Therefore, in terms of host response beta-defensins may be more suitable antimicrobial agents for clinical applications than alpha-defensins.

We have examined the expression of MIP-3alpha/CCL20 in oral squamous cell carcinoma (SCC) in vivo and in vitro. In addition, we have investigated whether the expression of MIP-3alpha/CCL20 is regulated by bacterial infection and inflammatory cytokines. In order to determine the mRNA level of MIP-3alpha, quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed with LightCycler using the double-stranded DNA dye, SYBR Green I. Oral epithelial cells and six SCC cell lines (SCC-9, SAS, BSC-OF, HSC-4, HSC, Ca9-22) were found to express MIP-3alpha mRNA. The expression of MIP-3alpha was upregulated by infection with Actinobacillus actinomycetemcomitans and by stimulation with lipopolysaccharide and TNF-alpha. By in situ hybridization, the detectable MIP-3alpha expression in SCC was localized primarily at the epithelial pearls corresponding to the spinous layer. These results suggest that MIP-3alpha contributes to the oral immunoresponse to bacterial infection, and may be involved in the growth of SCC.

Human beta-defensin(hBD)-2, an antimicrobial peptide, is produced by various epithelial cells. Because hBD-2 expression in the oral epithelium has not been assessed, we investigated its localization in normal oral epithelium and epithelial lesions. hBD-2 expression was studied using immunohistochemistry and in situ hybridization on formalin-fixed, paraffin-embedded tissue sections from 30 cases of squamous cell carcinoma and 6 cases of leukoplakia. Immunostaining for hBD-2 was more intense in hyperkeratinized than in ortho- or non-keratinized epithelium. In contrast, signals for hBD-2 mRNA were frequently stronger in non-keratinized epithelium than in hyper- or ortho-keratinized epithelium. The results suggest that keratinization in oral epithelium plays an important role in the biological function of hBD-2 both at the mRNA level and in the retention of the peptide in the epithelium.

Objective: Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma., Methods: One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses., Results: The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P<0.011 and P<0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival., Conclusions: The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma., (Copyright 1999 Academic Press.)

Human beta-defensin (hBD)-1 and hBD-2 are antimicrobial peptides that have been detected in certain types of epithelia, including the skin and oral epithelia. It has been suggested that bacterial infection is an important factor in the process of carcinogenesis. The expression of hBDs in oral squamous cell carcinoma (SCC) may be down-regulated. We studied the pattern of expression of hBD-1 and hBD-2 mRNA in oral (SCC) cell lines and in tumor samples obtained from four patients with oral SCC who underwent surgical resection, by reverse transcription-polymerase chain reaction (RT-PCR). Human gingival epithelial (HGE) cells were used as the control. The effect of various inflammatory cytokines on hBD-1 and hBD-2 expression in the HGE cells and SCC cell lines, was also studied. hBD-1 mRNA was detected in the Ca-9, SCC-9 and HSC-4 cell lines, but not in the SAS and KB cell lines. hBD-2 mRNA was detected in all five cell lines. All four tumor samples expressed both hBD-1 and hBD-2 mRNA, although the mRNA level of each protein varied. These results indicate that SCCs in which hBD expression is downregulated, may be susceptible to bacterial infection.

We have reported that a novel tumor-associated antigen (Ag), 22-1-1, was expressed in cancer cells derived mainly from the uterus and ovary [K. Sonoda et al., Cancer (Phila.), 77: 1501-1509, 1996]. The 22-1-1 Ag existed not only in adenocarcinomas but also in squamous cell carcinomas in the uterine cervix. Here, a relationship between tumor progression and invasion and 22-1-1 Ag expression was investigated in squamous cell neoplasms of the uterine cervix using immunohistochemical staining. The 22-1-1 Ag was not detected in normal uterine cervix (0 of 10 total cases) and dysplasias (0 of 47 total cases). However, 20% of carcinoma in situ (4 of 20 total cases) and 16.7% of microinvasive carcinomas (2 of 12 total cases) stained positively for 22-1-1 Ag. Moreover, areas depicting microinvasion on histology in uterine cancers (stage Ia) were more strongly stained than carcinoma in situ lesions. 22-1-1 Ag expression was found to be more frequent in invasive squamous cell carcinomas (82.6%; 57 of 69 total cases). The 22-1-1 Ag existed both in the cytoplasm and on the membrane of cancer cells. These findings suggest that 22-1-1 Ag expression might be related to tumor cell progression and invasion in the uterine cervical squamous cell epithelium.

Since it was first described in 1986, basaloid-squamous cell carcinoma (BSC) has been considered a distinct variant of squamous cell carcinoma that occurs in a variety of anatomic sites, including the head and neck region. We report the characterization of the first cell line established from a basaloid-squamous cell carcinoma of the floor of the mouth. The cell line exhibited a highly invasive capacity, indicating that BSC has very aggressive behavior. This cell line may be a useful model for elucidation of the biological characteristics of BSC.

Six hundred forty-seven cases of carcinoma of the uterine cervix with FIGO stages Ib or more were initially treated with hysterectomy at Kyushu University Hospital from 1973 to 1987. In these, 597 cases could be pathologically reviewed for ovarian metastasis. In these 597 cases, 335 were stage Ib, 71 IIa, 185 IIb, and 6 IIIb. Only 3 (0.5%) of 597 showed ovarian metastasis. All 3 cases were stage IIb. None of stage Ib cancer cases had ovarian metastasis. One (0.19%) of 524 squamous cell carcinomas metastasized to the ovary, whereas 2 (5.5%) of 36 pure adenocarcinomas revealed ovarian metastasis. Interestingly, all ovarian metastatic lesions were microscopic in size and found in the ovarian hilus. As for the primary lesion, all cases with ovarian metastasis showed deep myometrial invasion, corpus invasion, and lymphatic permeation. Two cases showed pelvic lymph node metastases and positive peritoneal washing cytology. From the results of our study, it can be said that it is fairly safe to preserve the ovary at the time of radical operation in squamous cell carcinoma of the uterine cervix, but it may not be safe to preserve the ovary in pure adenocarcinoma of the uterine cervix.

A case of glassy cell carcinoma of the endometrium in a 62-year-old woman is reported. Microscopically, a cytoplasm of ground-glass appearance was observed with a distinct cell wall and large nuclei containing prominent nucleoli. These histologic characteristics are consistent with those of glassy cell carcinoma of the cervix. Treatment consisted of total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection followed by external irradiation to the whole pelvis. The patient was alive without evidence of disease at 5 1/2 years.

From 1979 to 1986, 355 patients with cervical cancer underwent paraaortic lymph node (PAN) biopsy before the start of initial treatment. Nineteen of these 355 patients (5.4%) had a positive PAN, and the percentage incidence of positive PAN in each clinical stage was as follow: stage Ib, 2.4%; IIa, 0%; IIb, 3.7%; IIIb, 19.0%; and IV, 20%. Eighteen of these 19 patients also had positive pelvic lymph nodes. Positive PANs were found to be more frequent in cases of an adenocarcinoma than in cases of squamous cancer. The palpation of the PANs seemed to be too insufficient to predict the metastasis. Patients with positive PAN who had received paraaortic irradiation survived longer than those who did not receive such treatment. It is concluded that the evaluation of the PAN is important for the management of a cervical cancer.

During the past 15 years, 8 squamous cell carcinoma in situ and 21 invasive squamous cell carcinoma were treated in our department. Squamous cell carcinoma in situ was adequately treated by either wide local excision or CO2 laser vaporization. Radical vulvectomy was the main treatment modality in our department. Older patients tolerated well the surgery and had better outcome than those treated with radiotherapy alone. Histologically proven groin node metastasis was the risk factor to be overcome.

Eight cases of early adenocarcinoma selected from 101 adenocarcinomas of the uterine cervix were studied to establish the criteria of early adenocarcinoma. Lesions of these 8 cases were small in size. In 7 of 8 cases, these tumors originated in the area of the squamocolumnar junction (SCJ). Tumor cells consisted of two types of atypical columnar cells, i.e., tall columnar cells with enlarged and deeply eosinophilic cytoplasm and clear cells with enlarged and clear vacuoles. Tall columnar cells showed weak or negative reaction to high iron diamine (HID) stain and negative to Alcian blue (AB) stain. Clear cells showed negative reaction to HID stain and positive to AB stain. Although normal endocervical columnar cells showed markedly positive reaction to HID stain and negative reaction to AB stain, invasive adenocarcinoma cells showed similar reaction to early adenocarcinoma cells. From this study, it is surmised that early adenocarcinoma of the uterine cervix originates in the area of the SCJ and consists of tall cells in all cases and clear cells in 4 of 8 cases, and that HID-AB stain is useful in differentiating early adenocarcinoma cells from normal endocervical columnar cells.

Clinicopathologic features of 12 tumors of the lower uterine segment (isthmus) were studied and the findings compared with data on 196 tumors of the corpus endometrium proper. The mean age of these Japanese patients with tumors of the isthmus was 47 years and that of the patients with tumors of the corpus endometrium was 55 years. Seven of the isthmic tumors (58%) were graded as 3 (poorly differentiated) with histologic features of adenosquamous carcinoma, and all 12 tumors showed myometrial invasion. Endometrial hyperplasia or atypical endometrial glands were found in the endometrium adjacent to the tumor in 11 women. Normal mucosal structures of the lower uterine segment were uninvolved, in the area between the tumor and the endocervix, in only three patients. Four patients died of the disease within 36 months after surgery. In a comparison with the usual endometrial tumors of the corpus, tumors of the lower uterine segment tended to be high-grade adenosquamous carcinomas and myometrial invasion was more extensive. The short-term follow-up revealed that lower uterine segment tumors carried an unfavorable prognosis.