Quantitative morphology of primary and metastatic tumors: comparative studies on tissue sections

Feulgen-stained tissue sections of 84 invasive ductal carcinomas of the breast (IDC), 30 colorectal adenocarcinomas (ACC), 30 gastric adenocarcinomas (ACG), 10 lymph node metastases of squamous cell carcinomas (SCC) and 11 lymph node metastases of malignant melanomas (MM) were investigated by image cytometry at a spatial resolution of 0.25 micron. At least 150 tumor cell nuclei were measured in each case. By means of multivariate statistical analysis the specificity of the nuclear image for different histological tumor types could be demonstrated in lymph node metastases of SCC and MM. Nuclear image analysis therefore may be a useful tool for pathologists in making the differential diagnosis on metastases of unknown primary tumors. For IDC, ACG and ACC the metastatic phenotype could be identified by nuclear image analysis of the primary tumors. The prognostic significance of the nuclear image has been proved in adenocarcinomas of the stomach. Features of chromatin structure played an important role in both the diagnosis of doubtful histological tumor types and the prediction of lymph node involvement or prognostic outcome.     

Prognostic Significance of Peritumoral Lymphatic Vessel Density and Vascular Endothelial Growth Factor Receptor 3 in Invasive Squamous Cell Cervical Cancer

Cervical cancer is known to metastasize primarily by the lymphatic system. Dissemination through lymphatic vessels represents an early step in regional tumor progression, and the presence of lymphatic metastasis is associated with a poor prognosis. In patients who have undergone a radical hysterectomy, lymphovascular space invasion (LVSI), assessed on hematoxylin and eosin-stained slides, is a major factor for adjuvant therapy in patients with cervical cancer. With the advent of a lymphatic endothelial cell-specific marker, such as D2-40, it is now possible to distinguish between blood and lymphatic space invasion (LSI). In this study, the utility of D2-40 was assessed for the detection of lymphatic vessel density (LVD) and identification of LSI. The expressions of vascular endothelial growth factor receptor-3 (VEGFR-3), VEGF-C, tyrosine receptor kinase-2, and angiopoietin-1 were assessed by immunohistochemical methods on 50 patients with squamous cell carcinoma of the cervix. Clinicopathologic characteristics, including pelvic lymph node metastasis, were correlated with the above histochemical findings. We found that lymphangiogenesis, measured by an increase in peritumoral LVD, was significantly associated with positive lymph node status (P < .005). VEGFR-3 expression was significantly associated with LVD (P < .05). D2-40 staining verified LSI (P = .03) and surpassed that of hematoxylin and eosin-identified LVSI (P = .54). In conclusion, lymphangiogenic markers, specifically LVD quantified by D2-40 and VEGFR-3, are independently associated with LSI and lymph node metastasis in patients with early squamous cell carcinoma of the cervix treated with radical hysterectomy and pelvic lymphadenectomy.     

Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia

A. Repše‐Fokter, A. Pogačnik, V. Snoj, M. Primic‐Žakelj and M. S. Fležar
Review of negative and low‐grade cervical smears in women with invasive cervical cancer after the first 3 years of the national cervical screening programme in Slovenia Objective: The purpose of the study was to perform a national review of negative, low‐grade and inadequate smears reported during the latest screening period before cervical cancer diagnosis in 2006, after the first 3 years of the screening programme. Methods: Among 162 new cervical cancer cases there were 47 (29%) without previous cytology, 47 (29%) with one high‐grade smear prior to diagnosis and 68 (42.0%) with at least one previous negative, low‐grade, atypical or inadequate smear 1–40 months before diagnosis. Of the latter 68 cases, 37 patients with 59 smears (together with 118 control slides) were included in the review as 31 had smears reported at laboratories no longer operating. Findings were related to the last cytology report before diagnosis as well as to histological type and stage of the cancer. Results: In our study group, 19 (51%) of 37 patients had squamous cell carcinoma, 15 (41%) adenocarcinoma and 3 (8%) adenosquamous carcinoma, compared with 121 (75%), 26 (16%), 12 (7%), respectively, and 3 (2%) other types, for all carcinomas. Twenty‐one of 37 women also had high‐grade cytology prior to diagnosis of cancer. Women with previous cytology (with or without recent high‐grade smears) were more likely to have stage I cancers than those without cytology (P < 0.0001). The expert group upgraded 17/33 smears in the patients with squamous carcinomas, which was more than in those with adeno‐ and adenosquamous carcinomas (5/24, P < 0.05). Conclusion: As expected, a higher proportion of smears preceding adenocarcinomas were true negative. Under‐diagnosed smears were not related to cancer stage or last cytology report before diagnosis.     

Altered expression of sialyl-Tn,Lewis antigens and carcinoembryonic antigen between primary and metastatic lesions of uterine cervical cancers

Summary Immunohistochemical examination was performed of serial sections of 24 normal human adult cervical tissues and 53 human cervical carcinomas including 36 cases with lymph node metastasis. For this investigation, monoclonal antibodies directed to Lewis-X, Lewis-Y, sialyl-dimeric Lewis-X (SDLX), sialyl-Tn (STn) and carcinoembryonic antigen (CEA) were used. STn and CEA antigens were expressed very weakly in the normal cervical epithelium but strongly in the cancer cells, indicating the antigens to be oncogenic antigens of cervical squamous cell carcinoma. No significant difference in immunoreactivity was observed between primary and metastatic lesions of carcinoma or between primary lesions with and without metastasis. However, the expression patterns of STn and Lewis-Y antigens were quite different between primary lesions and metastatic lesions. In primary lesions the cancer cell nests tended to be stained centrally, but in metastatic lesions the cancer cell nests tended to be stained peripherally. This finding may reflect an important role of these carbohydrate chains in the process of metastasis of cervical squamous cell carcinoma to regional lymph nodes.     

Altered expression of sialyl-Tn, Lewis antigens and carcinoembryonic antigen between primary and metastatic lesions of uterine cervical cancers.

Immunohistochemical examination was performed of serial sections of 24 normal human adult cervical tissues and 53 human cervical carcinomas including 36 cases with lymph node metastasis. For this investigation, monoclonal antibodies directed to Lewis-X, Lewis-Y, sialyl-dimeric Lewis-X (SDLX), sialyl-Tn (STn) and carcinoembryonic antigen (CEA) were used. STn and CEA antigens were expressed very weakly in the normal cervical epithelium but strongly in the cancer cells, indicating the antigens to be oncogenic antigens of cervical squamous cell carcinoma. No significant difference in immunoreactivity was observed between primary and metastatic lesions of carcinoma or between primary lesions with and without metastasis. However, the expression patterns of STn and Lewis-Y antigens were quite different between primary lesions and metastatic lesions. In primary lesions the cancer cell nests tended to be stained centrally, but in metastatic lesions the cancer cell nests tended to be stained peripherally. This finding may reflect an important role of these carbohydrate chains in the process of metastasis of cervical squamous cell carcinoma to regional lymph nodes.     

The potential usefulness of monoclonal antibodies in the determination of histologic types of lung cancer in cytologic preparations

Two monoclonal antibodies (MAbs) were tested for their reactivity with antigens of exfoliated malignant cells in respiratory secretions of lung cancer patients. MAb CE 407 was developed from tissue culture cell line SW 756, derived from human uterine cervical squamous cell carcinoma; MAb BL 99-57 was developed from cell line T-24, derived from human transitional cell bladder cancer. MAb CE 407 reacted preferentially with squamous cell carcinomas (80%) and with some (44%) of the adenocarcinomas of the lung; BL 99-57 reacted with 76% of the adenocarcinomas, but only with 27% of the squamous cell carcinomas of the lung. The reactivity of BL 99-57 was more apparent in well-differentiated adenocarcinomas (89% positive), but less in poorly differentiated adenocarcinomas (65% positive). Neither of these antibodies reacted with antigens of small cell anaplastic carcinoma. These two MAbs may be useful in differentiating histologic types of lung cancer in cases that are difficult to diagnose morphologically and/or in which tissue is not available for study.     

Cell biologic properties in explant culture and heterotransplantation of malignant uterine cervical cells

The cell of origin of uterine cervical cancer was studied by using culture, enzyme histochemistry and heterotransplantation. Twenty-seven epidermoid carcinomas (8 large cell keratinizing squamous, 12 large cell nonkeratinizing squamous and 7 small cell nonkeratinizing squamous) and 2 adenocarcinomas of the uterine cervix were placed in culture. An outgrowth of carcinoma cells in vitro was observed in 22 of 29 cases: 6 keratinizing, 8 large cell nonkeratinizing and 6 small cell nonkeratinizing carcinomas and 2 adenocarcinomas. The squamous carcinomas showed a squamous-cell outgrowth pattern, except for one large cell nonkeratinizing and three small cell nonkeratinizing carcinomas that showed a glandular-cell outgrowth pattern. One of three keratinizing carcinomas was transplantable into the subcutis of BALB/c nude mice, producing keratinizing tumors; three of six large cell and one of three small cell nonkeratinizing carcinomas reproduced themselves, while the other two small cell carcinomas produced poorly differentiated adenocarcinomas in mice. The transplanted adenocarcinoma produced a well-differentiated adenocarcinoma resembling the original tumor. Small cell carcinomas and adenocarcinomas contained a heat-stable, L-phenylalanine-sensitive alkaline phosphatase. These results suggest that many uterine cervical cancers originate from the reserve cell.     

Immunohystochemical expression of cancer/testis antigens (MAGE-A3/4, NY-ESO-1) in non-small cell lung cancer: the relationship with clinical-pathological features

The aim of this study was to explore the expression of cancer/testis tumor associated antigens (C/T TAAs) MAGE-A 3/4 and NY-ESO-1 in lung squamous cell carcinoma and adenocarcinoma, and to evaluate their association with the standard clinical-pathological features of surgically treated lung cancer patients. The study included 80 patients with non-small cell lung cancer (40 adenocarcinomas, 40 squamous cell carcinomas) who had undergone surgery in the period between 2002 and 2005. The MAGE-A3/4 and NY-ESO-1 antigen expression was analyzed immunohistochemically (IHC). The results showed MAGE-A3/4 and NY-ESO-1 positive staining in 65.1% and 23.3% of squamous cell carcinomas and 18.9% and 10.8% of adenocarcinomas, respectively. A statistically higher MAGE-A3/4 expression was observed in planocellular bronchial carcinoma (p < 0.001), while no difference was found in the expression of NY-ESO-1 in adenocarcinoma and planocellular carcinoma (p = 0.144). A significant association was found between the MAGE-A3/4 expression and presence of tumor necrosis in squamous cell cancer specimens (p = 0.001), but not in adenocarcinoma (p = 0.033). A statistically significant association was noted between the NY-ESO-1 expression and positive hilar and mediastinal lymph nodes in adenocarcinoma (p = 0.025) whereas it was not the case in squamous cell carcinoma. Non-small cell lung cancer frequently expresses cancer/testis tumor associated antigens. Our results demonstrate that the MAGE-A3/4 and NY-ESO-1 expression was significant associated with prognostic factors of poor outcome of disease (presence of tumor necrosis and lymph node metastasis). As C/T antigens are important for inducing a specific immune reaction in lung cancer patients, there is an intention to form a subgroup of patients in the future, whose treatment would be enhanced by specific immunotherapy based on the observed scientific results.     

宫颈鳞状细胞癌中ADAM17 的表达及其临床意义

目的:探讨去整合素-金属蛋白酶17(ADAM17)在宫颈鳞状细胞癌中的表达及其临床病理意义。方法:运用免疫组织化学法分别检测正常宫颈上皮、宫颈鳞状细胞癌及宫颈上皮内瘤样变组织中ADAM17的表达,并分析其与宫颈癌临床分期及淋巴结转移的相关性。结果:ADAM17在正常宫颈上皮组织切片中无明显表达,在宫颈上皮内瘤样变组织中少部分表达,呈浅黄色,在宫颈鳞状细胞癌中癌细胞大量表达,ADAM17表达呈棕褐色,数量较多且浓染。不同临床分期的宫颈鳞状细胞癌组织中ADAM17的阳性表达率比较存在显著统计学差异(P0.05),且随临床分期的上升,ADAM17的表达逐渐升高;有淋巴结转移的宫颈鳞状细胞癌组织中ADAM17的阳性表达率显著高于无淋巴结转移的宫颈鳞状细胞癌组织,差异具有统计学意义(P0.05)。结论:ADAM17蛋白在宫颈鳞状细胞癌组织中呈异常高表达,且与宫颈鳞状细胞癌的临床分期和淋巴结转移密切相关,通过检测ADAM17蛋白的表达可能有助于宫颈鳞状细胞癌的诊断、治疗和预后预测。     

DNA cytometric analysis of surgically treated squamous cell cancer of the uterine cervix, stage pT1b1-pT2b

OBJECTIVE: To determine the utility of DNA content and DNA-related variables of proliferative activity regarding prognosis in cervical cancer. STUDY DESIGN: DNA image (ICM) andflow cytometry (FCM) were performed to determine the DNA index (DI), 5c-exceeding rate (5c-ER), S-phase fraction (SPF) and proliferation index (PI) in 163 patients with surgically staged pT1b1-pT2b squamous cell cancer of the uterine cervix and treated with primary radical hysterectomy. ICM was performed on imprint cytology, obtained from fresh tumor tissue, which was also used for FCM. Results were analyzed using the chi2 test and Cox regression analysis for risk of pelvic lymph node involvement, tumor recurrence and recurrence-free survival (RFS). RESULTS: ICM was performed on all 163 and FCM on 133 samples. One-third of the tumors showed DNA aneuploidy. Analysis demonstrated prognostic significance of a DI > or = 1.70, with a (70:30) 2.3-fold risk of recurrence (P=.024) and reduced RFS of 10 months (P=.003) in cases of DI > or = 1.70. A high 5c-ER > 11% was associated with pelvic lymph node involvement and decreased RFS (P < or = .04). Significantly more relapses were found in tumors with SPF > 12% (70.8% vs. 29.2%, P=.007). RFS was markedly reduced in tumors with high SPF (52.3 vs. 61.1 months, P=.011). Low proliferative tumors (PI<25%) were associated with lower stage (P=.036) and increased RFS (61.2 vs. 47.1 months, P=.028). In multivariate analysis of clinicopathologic variables (pT category, nodal status, lymphovascular space involvement) and DNA related variables, pelvic lymph node involvement was the only significant predictor of RFS. In patients with nodal involvement, tumors with DI >1.70 were associated with lessfavorable outcomes. CONCLUSION: DNA-related variables of cell cycle analysis were valuablefor predicting prognosis in cervical cancer patients. Tumors with DI>1.70, 5c-ER >11% and high proliferative activity (SPF>12%, PI>25%) represent a subgroup with a poor prognosis.     

Adenocarcinoma of the uterine cervix compared with squamous cell carcinoma: a 12-year study in Southampton and South-west Hampshire

In a 12-year study of the population of Southampton and South-west Hampshire (SSWH), there was no rise or fall in the incidence of adenocarcinoma of the uterine cervix, although the incidence of squamous cell carcinoma fell from 14 to 7.2 per 100000 women years and the overall fall in age-adjusted incidence of cervical carcinoma was commensurate with that of England and Wales. The majority (59%) of adenocarcinomas were seen in women aged less than 50, supporting the concept of a higher risk in young women. Screen-detected carcinomas accounted for 50% of adenocarcinomas and 41% of squamous cell carcinomas in women aged 20-64 (the difference was not significant). There were more screen-detected adenocarcinomas of less than 3 mm depth of invasion and 7 mm lateral extension during the third period of the study (1991-1993). The results are consistent with reports of an increased risk of cervical cancer in women born since 1940, and lesser effectiveness of screening in preventing adenocarcinoma compared with squamous cell carcinoma. High prevalence of early screen-detected carcinomas may have been a factor in recent reports of increased incidence of adenocarcinoma.     

Human papillomavirus prevalence among women with cervical intraepithelial neoplasia III and invasive cervical cancer from Goiânia,Brazil

This study estimated the prevalence and distribution of human papillomavirus (HPV) types among women with cervical intraepithelial neoplasia (CIN) grade III and invasive cervical cancer from Goi s (Brazil Central Region). Seventy-four cases were analyzed and consisted of 18 CIN III, 48 squamous cell carcinomas, 4 adenocarcinomas, 1 adenosquamous carcinoma and 3 undifferentiated carcinomas. HPV-DNA sequences were examined in formalin-fixed and paraffin-embedded tissues using primers from L1 region GP5+/GP6+. Polymerase chain reaction products were typed with dot blot hybridization using probes for HPV 16, 18, 31, 33, 45, 54, 6/11, 42/43/44, 51/52, 56/58. The prevalence of HPV was estimated to be 76% (56/74). HPV 16 was the most frequently found type, followed by HPV 33, 18 and 31. The prevalence of untyped HPV was 6%; 79% percent of the squamous cell carcinoma cases and 61% percent of the CIN III were positive for HPV and the prevalence rate of HPV types was the same for the total number of cases. According to other studies, HPV type 16 is the most prevalent virus in all Brazilian regions, but there is variation regarding to other types. Type 18 is the second most prevalent HPV in North, Southeast and South Brazil regions and types 31 and 33 are the second most prevalent HPV in Northeast and Central Brazil, respectively.     

Cervicovaginal cytology in uterine adenocarcinoma and adenosquamous carcinoma. Comparison of cytologic and histologic findings

To investigate the diagnostic accuracy and to characterize the findings in false-negative cases, the results of cervicovaginal cytology in 56 adenocarcinomas and 25 adenosquamous carcinomas (42 cervical, 36 endometrial, 2 metastatic and 1 arising synchronously from both cervix and endometrium) were reviewed, including review of the actual slides in 56 cases. Overall, 80% of the initial cytologic diagnoses resulted in diagnostic curettage (i.e., cytology was effectively positive); 84% of the postreview diagnosis were effectively positive. Nine cytology slides showed no malignant cells; eight of these negative smears showed repair, five were atrophic, two showed a high estrogen effect and one had enlarged atypical bare nuclei. These false-negative diagnoses were associated with an endometrial primary site (P less than .01), endometrioid histology (P less than .005), low-grade or intermediate-grade histology (P less than .005), small size of tumor (P less than .05) and absence of cervical involvement (P less than .005) in those cases in which a hysterectomy was performed. False-negative diagnoses were not associated with an absence of endocervical cells or with scanty cellularity. Of 39 cervical and 28 endometrial carcinomas with a positive cytologic diagnosis (initially or after review of the available slides), cytology correctly identified the primary site in 18% and 54% of the cases, respectively. Cytology incorrectly classified the anatomic site of four cervical and three endometrial carcinomas and considered one case arising in both the endometrium and cervix to be endometrial. Routine cervicovaginal cytology does have a role in screening for uterine glandular carcinoma; to maximize its diagnostic sensitivity, we suggest using a recommendation for curettage in the report of positive cases so that all of the varied cytologic diagnoses associated with glandular carcinomas will receive a uniform clinical response. In those cases with preserved cancer cells, a correlation can be made with the histologic type of the carcinoma, rather than with the anatomic site.     

Loss of Heterozygosity and Copy Number Alterations in Flow-Sorted Bulky Cervical Cancer

Treatment choices for cervical cancer are primarily based on clinical FIGO stage and the post-operative evaluation of prognostic parameters including tumor diameter, parametrial and lymph node involvement, vaso-invasion, infiltration depth, and histological type. The aim of this study was to evaluate genomic changes in bulky cervical tumors and their relation to clinical parameters, using single nucleotide polymorphism (SNP)-analysis.Flow-sorted tumor cells and patient-matched normal cells were extracted from 81 bulky cervical tumors. DNA-index (DI) measurement and whole genome SNP-analysis were performed. Data were analyzed to detect copy number alterations (CNA) and allelic balance state: balanced, imbalanced or pure LOH, and their relation to clinical parameters.The DI varied from 0.92–2.56. Pure LOH was found in ≥40% of samples on chromosome-arms 3p, 4p, 6p, 6q, and 11q, CN gains in >20% on 1q, 3q, 5p, 8q, and 20q, and losses on 2q, 3p, 4p, 11q, and 13q. Over 40% showed gain on 3q. The only significant differences were found between histological types (squamous, adeno and adenosquamous) in the lesser allele intensity ratio (LAIR) (p = 0.035) and in the CNA analysis (p = 0.011). More losses were found on chromosome-arm 2q (FDR = 0.004) in squamous tumors and more gains on 7p, 7q, and 9p in adenosquamous tumors (FDR = 0.006, FDR = 0.004, and FDR = 0.029).Whole genome analysis of bulky cervical cancer shows widespread changes in allelic balance and CN. The overall genetic changes and CNA on specific chromosome-arms differed between histological types. No relation was found with the clinical parameters that currently dictate treatment choice.     

Bcl-2和COX-2在宫颈鳞癌中的表达及其临床意义

目的：观察Bcl-2和COX-2在正常宫颈和宫颈鳞癌中的表达情况,并探讨其与宫颈鳞癌发生发展的关系。方法：应用免疫组织化学s-P法检测40例宫颈鳞癌组织、10例正常宫颈组织中Bcl-2和COX-2的表达情况。结果：（1）Bcl-2在正常宫颈组织和宫颈鳞癌组织中的阳性表达率分别为30．0％、72．5％（P〈0．05）,而COX-2在正常宫颈组织和宫颈鳞癌组织中的阳性表达率分别为0．0％、60．0％（P〈0．05）。（2）在宫颈鳞癌中,Bcl-2的表达与宫颈鳞癌的病理分级、临床分期以及淋巴结转移无关（P〉0．05）,而COX-2的表达与宫颈鳞癌的病理分级及淋巴转移有关（P〈0．05）,与临床分期无关（P〉0．05）。（3）Spearman等级相关性分析显示宫颈鳞癌组织中Bcl-2和COX-2的表达呈正相关（r=0．517,P〈0．01）。结论：Bcl-2和COX-2在宫颈鳞癌中的表达升高并呈显著正相关,且COX-2的表达与宫颈鳞癌的淋巴转移有关,二者在宫颈癌的发生发展中可能起重要作用,有可能作为评估宫颈鳞癌淋巴结转移的参考指标。     

Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology

A. Talaat, D. Brinkmann, J. Dhundee, Y. Hana, J. Bevan, R. Irvine, S. Bailey and R. Woolas
Risk of significant gynaecological pathology in women with ?glandular neoplasia on cervical cytology Objective: To review the risk of pre‐invasive and invasive gynaecological pathology in women referred with cervical cytology reporting ?glandular neoplasia. Methods: Review of the case notes of all women referred with cervical cytology reported as ?glandular neoplasia between January 1999 and December 2008 at two UK hospitals: Portsmouth Hospitals NHS Trust and Queen Mary’s Hospital Sidcup. The category of ‘borderline nuclear change in endocervical cells’, result code 8 according to the national health service cancer screening programme (NHSCSP), was excluded from the study. Results: A total of 200 women were identified using the hospitals’ pathology computer systems. Invasive carcinoma was found in 48 women (24%): 28 endocervical adenocarcinomas, eight squamous cell carcinomas (SCC), ten endometrial and two ovarian adenocarcinomas. Pre‐invasive neoplasia was found in 115 (57.5%), including 14 cervical glandular intraepithelial neoplasia (CGIN), 31 cervical intraepithelial neoplasia (CIN) grade 2/3 and 70 concomitant CGIN and CIN2/3. CIN1/HPV was found in 25, simple endometrial hyperplasia in three and no histological abnormality in three. Thirty‐four (70.8%) of 48 invasive carcinomas (of which 23 were endocervical adenocarcinomas) were in asymptomatic women investigated for abnormal cytology. Fourteen of 34 (41.4%) of those with ?glandular neoplasia thought to be endometrial were CGIN or CIN2/3. Colposcopic appearances were normal in 47.6% of women with pure cervical glandular neoplasia (adenocarcinoma or CGIN) compared with 12.8% with squamous cell lesions (CIN2/3 or SCC): P = 0.0001. Thus, colposcopy was more sensitive for detecting squamous cell abnormalities than their glandular counterparts. Although cervical adenocarcinomas are less amenable to prevention by screening than cervical SCC, in our study cervical cytology predominantly detected these abnormalities at their early asymptomatic stages. Conclusion: At least CIN2 was found in 81.5% in women referred with cervical cytology reporting ?glandular neoplasia. A thorough evaluation of the whole genital tract is needed if colposcopy is negative.     

Applicability of Preoperative Nuclear Morphometry to Evaluating Risk for Cervical Lymph Node Metastasis in Oral Squamous Cell Carcinoma

Background

We previously reported the utility of preoperative nuclear morphometry for evaluating risk for cervical lymph node metastases in tongue squamous cell carcinoma. The risk for lymph node metastasis in oral squamous cell carcinoma, however, is known to differ depending on the anatomical site of the primary tumor, such as the tongue, gingiva, mouth floor, and buccal mucosa. In this study, we evaluated the applicability of this morphometric technique to evaluating the risk for cervical lymph node metastasis in oral squamous cell carcinoma.

Methods

A digital image system was used to measure the mean nuclear area, mean nuclear perimeter, nuclear circular rate, ratio of nuclear length to width (aspect ratio), and nuclear area coefficient of variation (NACV). Relationships between these parameters and nodal status were evaluated by t-test and logistic regression analysis.

Results

Eighty-eight cases of squamous cell carcinoma (52 of the tongue, 25 of the gingiva, 4 of the buccal mucosa, and 7 of the mouth floor) were included: 46 with positive node classification and 42 with negative node classification. Nuclear area and perimeter were significantly larger in node-positive cases than in node-negative cases; however, there were no significant differences in circular rate, aspect ratio, or NACV. We derived two risk models based on the results of multivariate analysis: Model 1, which identified age and mean nuclear area and Model 2, which identified age and mean nuclear perimeter. It should be noted that primary tumor site was not associated the pN-positive status. There were no significant differences in pathological nodal status by aspect ratio, NACV, or primary tumor site.

Conclusion

Our method of preoperative nuclear morphometry may contribute valuable information to evaluations of the risk for lymph node metastasis in oral squamous cell carcinoma.     

Tissue expression of VEGF as a prognostic factor in early cervical squamous cell carcinoma

The purpose of this retrospective study was to determine whether the intensity of tumor angiogenesis, expressed as microvessel density (MD), is indeed an important parameter predicting lymph node metastasis and survival rate in 73 women operated on for early invasive squamous cell carcinoma of the uterine cervix in stages Ib and IIa (FIGO). Angiogenesis was quantified by light microscope (LM) using an assay for vascular endothelial growth factor (VEGF). In the study, differences were revealed by comparing the MD between both groups. The patient survival with high MD was significantly worse than for those with low MD (p<0.01). A correlation was found between MD and the incidence of lymph node metastases. Hence, quantitative analysis of MD used as the expression of VEGF in the each cervical squamous cell carcinomas could be useful as a significant prognostic indicator.     

Clinical Features in Differentiated Thyroid Carcinoma Stratified By Lymph Node Status

Objective: Cervical lymph node (CLN) metastases (mets) often occur in differentiated thyroid cancer (DTC), especially in the central compartment, and are a major predictor of local recurrence. We examined clinical endpoints in three groups of patients based on status of lymph node involvement: those with definite lymph node involvement (N1), negative lymph nodes (N0), and no lymph nodes resected (Nx). We correlated these endpoints with clinical and pathologic features of these patients.Methods: Medical records of 261 patients with DTC who underwent thyroidectomy between 2006 and 2018 at our center were reviewed. Lymph node status of patients was categorized based on American Joint Committee on Cancer (AJCC) 8th edition criteria as N1, N0, and Nx. We performed statistical analysis to assess the differences among these groups, using one-way analysis of variance. When significant differences were found, pairwise comparisons were conducted among the three groups. Statistical significance was defined as 2-tailed P<.05 for all tests.Results: There were significant differences among the groups in tumor multicentricity, tumor category/size, AJCC stage, and the presence of thyroglobulin auto-antibodies (TgAbs). There were no difference in age, gender, or histopathology. N1 patients had a higher incidence of multicentricity, larger tumor sizes, and were more likely to have elevated TgAbs. There were no significant differences between the N0 and Nx groups.Conclusion: This study shows that larger and multi-centric tumors are associated with increased likelihood of CLN mets in DTC. We suggest increased vigilance for CLN mets in tumors >2 cm, multicentric tumors, and patients with elevated TgAbs.Abbreviations: AJCC = American Joint Committee on Cancer; CLN = cervical lymph node; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; mets = metastases; N0 = no cancer in any lymph nodes; N1 = cancer in a lymph node; N1a = cancer in a central compartment lymph node; N1b = cancer in a lateral neck lymph node; Nx = lymph nodes not resected or examined; PTC = papillary thyroid cancer; TgAb = thyroglobulin auto-antibody